Ciprofloxacin

Diagn Microbiol Infect Dis, 1990 Mar-Apr, 13(2), 115 - 26
Pharmacokinetic behavior of ciprofloxacin both in native cardiac and porcine valves treated in glutaraldehyde; Kalmar P et al.; When judging a probable therapeutic success for antibiotic management of bioprosthetic endocarditis, sufficient drug levels in heterologous valve tissues play a very important role . The pharmacokinetic behavior of ciprofloxacin was investigated in native and porcine valvular tissues and compared with plasma levels during a 90- to 120-min period of surgery . Analysis was carried out by HPLC using excised valvular tissues (Hancock T 505) . In all, 15-20 patients were investigated in each group . The antibiotics were administered intravenously or per os . Tissue concentrations after onset of the procedures showed ciprofloxacin plasma concentrations of 2.09-0.47 micrograms g in the native and 3.98-1.99 micrograms/g in the heterologous valvular tissues.

Mol Microbiol, 1990 Mar, 4(3), 345 - 53
Escherichia coli cells resistant to the DNA gyrase inhibitor, ciprofloxacin, overproduce a 60 kD protein homologous to GroEL; Hallett P et al.; Using a variety of mutagenic methods, we have generated a series of ciprofloxacin-resistant mutants derived from Escherichia coli strains which overproduce the DNA gyrase A protein . Many of these mutants are found to overexpress a 60 kD protein which is shown to be highly homologous in terms of N-terminal amino acid sequence to the E . coli heat-shock protein, GroEL . Other evidence confirms that the 60 kD protein is unrelated to DNA gyrase and is similar, but not identical, to GroEL.

Clin Pharmacokinet, 1990 Mar, 18(3), 210 - 9
Effects of antacids on the clinical pharmacokinetics of drugs . An update; Gugler R et al.; Since a previous review by Hurwitz was published in 1977 a large number of reports on drug interactions with antacids have appeared, few of which are of clinical relevance . Tetracyclines form insoluble complex molecules by metal ion chelation with various antacids; tetracycline absorption may be decreased by more than 90% by this interaction . Of the new class of quinolone antibiotics, the absorption of ciprofloxacin and ofloxacin is reduced by 50 to 90% in the presence of aluminium- and magnesium hydroxide-containing antacids . In contrast to early work showing inhibition of the absorption of beta-adrenergic blocking drugs by antacids, subsequent studies did not confirm a reduction in the bioavailability of either atenolol or propranolol during antacid treatment; indeed, they showed an increase in the plasma concentrations of metoprolol when the drug was coadministered with an antacid . The bioavailability of captopril was significantly reduced in the presence of an antacid, and lower plasma concentrations of this angiotensin-converting enzyme inhibitor were accompanied by a reduction of its effect on the systolic blood pressure of the patients . The absorption of the cardiac glycosides digoxin and digitoxin is not inhibited by antacids to a significant degree, although earlier studies had shown a positive effect when the dissolution of the glycoside preparations was relatively poor . Antacids reduce the bioavailability of the H2-receptor antagonists cimetidine and ranitidine only when high antacid doses are used and when the drugs are administered simultaneously . The bioavailability of famotidine was not significantly altered by a potent antacid preparation, although a trend towards reduced absorption was observed . Iron absorption is significantly decreased in the presence of sodium bicarbonate and calcium carbonate, but is nearly complete when coadministered with aluminium-magnesium hydroxide . Nonsteroidal anti-inflammatory drugs such as naproxen, tenoxicam, ketoprofen, ibuprofen and piroxicam are not affected in their absorption by antacid treatment . Theophylline bioavailability is unchanged when the drug is given together with antacids, although its rate of absorption may be altered, leading to a reduction or an increase in the time of the occurrence of peak plasma drug concentrations.

Pneumologie, 1990 Feb, 44 Suppl 1, 312 - 3
{Bronchopulmonary penetration of ciprofloxacin}; Loos U et al.; We determined ciprofloxacin levels in plasma, saliva, bronchial secretions, lavage fluid, and alveolar macrophages in 9 patients five hours following the last administration of the drug (2 x 750 mg ciprofloxacin daily over a period of at least 3 days) . The ciprofloxacin concentration in the alveolar film was determined using urea as internal marker for the lavage . On average it was 2.51 micrograms/ml (= 186% of the plasma level), and clearly exceeded the minimal inhibition concentrations for the facultative pathogenic organism . This means that, in the alveolar film--which represents the barrier to descending pneumonia--an effective accumulation of the quinolone takes place.

DICP, 1990 Feb, 24(2), 138 - 40
Potential neurologic toxicity related to ciprofloxacin; Schwartz MT et al.; A 74-year-old woman with multiple medical problems including chronic renal failure was admitted for treatment of a diabetic foot infection . On day 12 of therapy with oral ciprofloxacin and metronidazole, the patient experienced generalized myoclonus and muscle twitching . At that time it was realized that although the ciprofloxacin regimen prescribed was a usual dose for a skin and soft-tissue infection, it was excessive for her degree of renal function . This was thought to be the most likely cause of the patient's neurotoxicity . Seizure activity has been reported to occur with the quinolone antibiotics and, with the increasing use of these agents, dose reductions should be kept in mind to avoid potentially serious adverse reactions.

J Med Microbiol, 1990 Jan, 31(1), 65 - 70
DNA breakdown by the 4-quinolones and its significance; Lewin CS et al.; DNA breakdown occurred in Escherichia coli KL16 exposed to nalidixic acid, ciprofloxacin or norfloxacin . However DNA breakdown does not seem to be the cause of the lethality of the 4-quinolones because it still occurred under conditions which abolished the lethality of nalidixic acid . Furthermore, no correlation was found between the amount of DNA breakdown and the rate of death of bacteria caused by the three 4-quinolones . Similarly, DNA breakdown did not occur when recB or recC mutants were treated with nalidixic acid despite both mutants being killed by the drug, again suggesting that DNA breakdown is not the cause of bacterial death . Since recB and recC mutants lack exonuclease V, this enzyme may be responsible for the DNA breakdown observed in bacteria treated with 4-quinolones.

DICP, 1990 Jan, 24(1), 27 - 8
Possible interaction between ciprofloxacin and warfarin; Kamada AK; A 72-year-old man had been taking warfarin for a pulmonary embolus and recurrent deep-vein thromboses . His prothrombin times (PTs) were maintained between 15 and 18 sec (PT ratio 1.25-1.5 x control) for several months on a dose of warfarin 2.5 mg/d . Six weeks prior to starting ciprofloxacin 500 mg bid, the patient's PT was 15.5 sec (Pt ratio 1.29 x control) . After one week of ciprofloxacin, his PT had increased to 22 sec (PT ratio 1.83 x control) . No other causes for the increase were apparent . It is recommended that patients receiving both medications have their prothrombin times carefully monitored and warfarin doses adjusted only as necessary.

Orthopedics, 1990 Jan, 13(1), 55 - 60
Oral ciprofloxacin for osteomyelitis; MacGregor RR et al.; Ciprofloxacin is a new, oral, broad spectrum fluoroquinolone antibiotic which has a long serum half-life, a low incidence of significant adverse reactions, and is administered twice daily . Eighteen patients with osteomyelitis were treated with ciprofloxacin, 750 mg orally twice daily . The mean age of the patients was 43 years (range, 21 to 73 years); 12 were men . The duration of treatment ranged from 5 to 52 weeks (mean, 20.0 +/- 15.7 weeks) . At follow up (mean, 18 +/- 8.5 months; range, 4 to 34.5 months), 11 patients (61.6%) achieved arrest of infection, 4 (22.2%) had improved with therapy, and 3 (16.6%) failed to improve . Ciprofloxacin was well tolerated . Four case histories are given.

Pharmacotherapy, 1990, 10(5), 337 - 40
Renal dysfunction associated with ciprofloxacin; Hatton J et al.; We cared for a 64-year-old woman who experienced increased serum creatinine levels after 8 days of ciprofloxacin therapy . She had previously received a course of several antibiotics, including gentamicin . Renal function returned to normal 18 days after the ciprofloxacin was discontinued . This is the eighth reported case of nephrotoxicity associated with this agent . The mechanism and predisposing factors have not been defined.

Eur Urol, 1990, 17 Suppl 1, 46 - 51
Safety profile of quinolones; Shah PM et al.; Tolerability data from reports to Federal Drug Authorities, information from drug companies, medical literature, and personal experience are cited . Tolerability data regarding norfloxacin were derived from more than 31,000 patients in a phase IV study; ofloxacin from more than 14,000 patients in a phase IV study; and ciprofloxacin from more than 8,000 patients during phase II and phase III studies . Adverse experiences occurred in 6.8% of patients treated with norfloxacin, 9.1% with ciprofloxacin, and 9.3% with ofloxacin . The most frequent adverse effects involved the gastrointestinal tract . Untoward effects were generally mild and reversible when therapy was discontinued.

Pharmacotherapy, 1990, 10(2), 154 - 6
Oral clindamycin and ciprofloxacin therapy for diabetic foot infections; Sesin GP et al.; Infected foot ulcers are a common complication in persons with diabetes . In general, treatment consists of intravenous administration of antibiotics, for which the patients are customarily hospitalized . The average length of hospital stay for this therapy in our institution is 15.6 days . We evaluated a regimen of oral clindamycin plus ciprofloxacin, which patients could take at home, with respect to the clinical eradication of the infection and treatment cost savings . Our results demonstrated that with these oral agents, patients' length of hospital stay was greatly reduced, and the pharmacy realized significant cost avoidance.

Scand J Infect Dis, 1990, 22(1), 75 - 8
Treatment of experimental Escherichia coli pyelonephritis in rat by ciprofloxacin in comparison with tobramycin; Lecomte F et al.; The ciprofloxacin efficacy was compared to that of tobramycin in an Escherichia coli pyelonephritis model in rat . Treatments started 48 h after ligation of the left ureter and inoculation of the bladder and continued for 5 days . Ciprofloxacin (2.5 mg/kg/d and 10 mg/kg/d) was administered intravenously either in a single daily dose or in 2 divided doses at 12 h intervals . Tobramycin (2.5 mg/kg/d and 10 mg/kg/d) was administered by the intramuscular route, in a single daily dose . Ciprofloxacin 10 mg/kg/d was as efficacious as tobramycin irrespective of dosage schedule . Ciprofloxacin 2.5 mg/kg/d was more effective when given twice a day than once.

Eur J Clin Pharmacol, 1990, 39(1), 63 - 9
Pharmacokinetic determination of relative potency of quinolone inhibition of caffeine disposition; Barnett G et al.; Quinolone is reported to interact with caffeine, often resulting in an increase both in the plasma half-life and AUC, a decrease in total plasma clearance, and little change in the absorption rate constant and maximum plasma level . These complex changes in the pharmacokinetics of caffeine were analyzed experimentally and from published reports in order to determine the nature of the interaction, which is thought to be due to inhibition of caffeine metabolism by quinolones . A simple pharmacokinetic model for the caffeine-quinolone interaction was developed, which provides a unified method for evaluation and comparison of the effect of quinolones on the disposition of caffeine . The model is applicable to other methylxanthines, such as theophylline . The relative potency of the interactions of quinolones with caffeine in humans has been established as enoxacin (100), pipemidic acid (29), ciprofloxacin (11), norfloxacin (9) and ofloxacin (0).

Dermatologica, 1990, 181(2), 98 - 103
Demonstration of quinolone phototoxicity in vitro; Przybilla B et al.; The 'first-generation' quinolones cinoxacin, nalidixic acid, oxolinic acid, pipemidic acid and rosoxacin and the newly developed quinolones ciprofloxacin, enoxacin, fleroxacin, norfloxacin and ofloxacin were screened in vitro at 10(-5), 10(-4) and 10(-3) M concentrations for ultraviolet (UV)-induced phototoxic effects in a photohemolysis test . At 10(-3) M, photodependent effects of norfloxacin could not be evaluated, as hemolysis occurred without irradiation . All other compounds with the exception of ciprofloxacin were found to be phototoxic at 10(-3) M and some also at 10(-4) M . Hemolysis was UV dose dependent and for all compounds most prominent after exposure to UVA-rich radiation except for fleroxacin which was most active in the UVB range . Besides fleroxacin, also oxolinic acid, pipemidic acid and rosoxacin induced hemolysis with irradiations rich in UVB . It is concluded that quinolones have to be regarded as potentially phototoxic substances . Therefore intense light exposure should be avoided during treatment with these agents.

Cancer Chemother Pharmacol, 1990, 26(6), 423 - 8
Ability of four potential topoisomerase II inhibitors to enhance the cytotoxicity of cis-diamminedichloroplatinum (II) in Chinese hamster ovary cells and in an epipodophyllotoxin-resistant subline; Eder JP et al.; Four drugs known to interact with topoisomerase II were assessed for their ability to enhance the cytotoxicity of cis-diamminedichloroplatinum(II) (CDDP) in Chinese hamster ovary (CHO) cell lines sensitive and resistant to VM-26 . The combination treatments were analyzed by isobologram methodology . On 24 h exposure, there was no significant difference in the cytotoxicity of novobiocin or ciprofloxacin toward either cell line . The resistant cells were approximately 9-fold more resistant to 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) and approximately 170-fold more resistant to etoposide after a 24-h exposure . The combination of novobiocin and cisplatin produced greater than additive cell kill over the entire dose range of cisplatin tested in both cell lines . m-AMSA and CDDP produced cell kill that fell within the envelope of additivity . Etoposide and CDDP resulted in cytotoxicity that was slightly greater than additive at low CDDP concentrations and additive at the highest concentration of CDDP tested in the parental cell line and was slightly greater than additive in the resistant cell line . Ciprofloxacin and CDDP, like novobiocin, resulted in greater than additive cell kill in both cell lines . The enhancement of CDDP cytotoxicity by novobiocin that was seen in exponentially growing cells was lost in stationary-phase cultures . In these studies, novobiocin and, to a lesser degree, ciprofloxacin produced greater than additive cell kill in combination with CDDP in parental and epipodophyllotoxin-resistant CHO cells.

Adv Exp Med Biol, 1990, 277, 683 - 90
Severity of oxygen free radical effects after ischemia and reperfusion in intestinal tissue and the influence of different drugs; Lutz J et al.; The influence of different drugs on ischemia induced oxygen free radical damage was examined in intestinal tissue of rats by determination of thiobarbituric acid reactive substances (TBARS) . Some methodical aspects of this method were considered . Experiments were done with and without the use of polymerized stromafree hemoglobin (PHb) as an additional oxygen carrier . Reversible total occlusion of the superior mesenteric artery was performed for 90 min, reperfusion time was 2.5 hours . Despite higher O2 availability PHb did not increase the TBARS level any further . Superoxide dismutase with catalase; allopurinol; ciprofloxacin; and deferoxamine produced a highly significant reduction of TBARS, even if used together with PHb.

Am J Nephrol, 1990, 10(5), 416 - 21
Gallium scan in the diagnosis and treatment of renal malacoplakia; Curran KA et al.; A middle-aged female was admitted with a presumptive diagnosis of pyelonephritis that failed to respond to conventional antibiotic therapy . Multiple investigations to define the etiology of the persistent fever and accompanying acute renal failure were negative . A gallium scan revealed intense uptake in the renal parenchyma . Percutaneous renal biopsy revealed malacoplakia . Six weeks of therapy with ciprofloxacin resulted in resolution of fever, improvement in the follow-up gallium scan, and reversal of the acute renal failure.

Int J Immunopharmacol, 1990, 12(1), 31 - 6
Effects of quinolones on tumor necrosis factor production by human monocytes; Bailly S et al.; Previous studies have shown that in lipopolysaccharide (LPS)-stimulated human monocytes, interleukin 1 (IL-1) production is altered by quinoline derivative antibiotics (quinolones), in a way which depends both on the dose and on the agents used . Given that IL-1 and tumor necrosis factor alpha (TNF) are produced in response to LPS and have some overlapping and synergistic activities, we sought to determine if TNF production was altered under the above-mentioned conditions . We investigated the effects of three quinolones: ciprofloxacin (Cip), pefloxacin (Pef) and ofloxacin (Ofl) . These quinolones were found to decrease extracellular TNF production in a dose-dependent manner at concentrations higher than 25 micrograms/ml as previously described by our laboratory with regard to IL-1 production . Moreover, the order of the extracellular decrease in TNF and IL-1 induced by each drug was similar . However, in contrast to IL-1 activity, the quinolones studied also reduced cell-associated TNF . The kinetics of TNF production suggested that the quinolones affected TNF production at a very early step, probably during TNF synthesis rather than during its secretion into the extracellular medium . Furthermore, the quinolone-induced accumulation of intracellular cAMP could explain the extracellular decrease in both IL-1 and TNF production.

J Antimicrob Chemother, 1989 Dec, 24(6), 863 - 73
The effect of mutations in the SOS response on the kinetics of quinolone killing; Walters RN et al.; The SOS response is induced in Escherichia coli by agents that damage DNA, such as quinolone antibiotics . It has been proposed that induction of the SOS response by these agents may have a role in the mechanism of quinolone action . SOS mutants derived from Escherichia coli AB1157 were investigated by susceptibility testing and killing kinetic studies at various quinolone concentrations to determine whether SOS response induction was protective or damaging to quinolone-treated bacteria . Susceptibility testing showed some differences between the SOS mutants, but killing kinetic studies demonstrated further differences, some of which could be explained with respect to the SOS phenotype . The effect of ciprofloxacin and nalidixic acid on the mutants cannot be explained with respect to the SOS phenotype, although the presence of a defective SOS response makes the bacteria less sensitive to the action of these agents . Evidence is provided that the induction of the SOS response may be protective to fleroxacin and enoxacin treated bacteria . These results suggest that quinolones may not have a common mechanism of action, as was first thought.

Clin Pharmacol Ther, 1989 Dec, 46(6), 700 - 5
Effects of aluminum and magnesium antacids and ranitidine on the absorption of ciprofloxacin; Nix DE et al.; The effect of an antacid (Maalox) and ranitidine administration on the absorption of ciprofloxacin was evaluated in healthy male volunteers who were enrolled in three separate studies . Each study was designed at a three- or four-period crossover and included the administration of 750 mg ciprofloxacin alone as a control treatment . Treatments that were evaluated included the administration of ciprofloxacin 5 to 10 minutes, 2 hours, 4 hours, and 6 hours after a single 30 ml dose of antacid; the administration of antacid 2 hours after ciprofloxacin was given; and the administration of ciprofloxacin 2 hours after a 200 mg ranitidine tablet . Administration of antacid within 4 hours before ciprofloxacin dose resulted in a significant decrease in ciprofloxacin absorption (p less than 0.05) . Percentages of relative bioavailability compared with control values were 15.1%, 23.2%, and 70% for the 5 to 10 minute, 2 hour, and 4 hour antacid pretreatments, respectively . Administration of antacid 6 hours before or 2 hours after the ciprofloxacin dose did not affect absorption . Ranitidine did not alter ciprofloxacin absorption . Antacids that contain magnesium and aluminum salts may reduce the absorption of ciprofloxacin . The extent of this interaction appears to increase as the time between administration of the two drugs decreases . Ranitidine is suggested as an alternative to antacids for patients receiving treatment with ciprofloxacin.

Am J Med, 1989 Nov 30, 87(5A), 98S - 102S
Safety of oral ciprofloxacin . An update based on clinical trial results; Schacht P et al.; The safety of ciprofloxacin was established on a data base (compiled through the end of 1988) of 9,473 well-documented treatment courses world-wide . The daily dosages ranged between 200 and 2,000 mg orally . Thirty-eight percent of the patients received doses between 1 and 10 mg/kg body weight, 46 percent between 11 and 20 mg/kg, and the remaining 16 percent more than 20 mg/kg body weight daily . Ciprofloxacin was administered to 4,214 women (45 percent) and 5,252 men (55 percent) . The duration of treatment ranged from less than two days to more than 90 days . A 600-mg daily dose of ciprofloxacin was used mostly in Japan (2,341 patients) . The daily dose of 1,000 mg was administered chiefly in the United States and Europe (2,288 patients) . The age of the patients ranged from less than one year to 99 years (mean, 50.6 years) . More than 38 percent were older than 60 years . According to COSTART terminology, the following drug-related side effects were observed in the different organ systems: digestive, 4.9 percent; metabolic-nutritional, 4.4 percent; central nervous system, 1.5 percent, skin, 1.1 percent; hemic and lymphatic, 0.9 percent; urogenital, 0.8 percent; body as a whole, 0.5 percent; cardiovascular, 0.2 percent; special senses, 0.2 percent; musculoskeletal, 0.1 percent; and respiratory, 0.1 percent . Several patients had more than one reaction . The total incidence of side effects for the treated patients was 9.3 percent . The vast majority of adverse reactions were mild or moderate (94 percent) . Serious side effects were reported for 55 patients (6 percent) . Based on the 9,473 courses, the incidence of severe reactions was 0.6 percent . Ciprofloxacin treatment was discontinued due to side effects in 146 patients (1.5 percent), mostly due to gastrointestinal reactions (80 patients) . The worldwide data from clinical trials with oral ciprofloxacin clearly demonstrate that the drug is relatively safe, and the side effects are usually mild or moderate in intensity and are reversible.

Am J Med, 1989 Nov 30, 87(5A), 92S - 97S
Safety of intravenous ciprofloxacin . A review; Arcieri GM et al.; Data from 1,878 courses of intravenous ciprofloxacin therapy, administered to 1,869 patients in 59 clinical trials, were analyzed for drug safety . The 985 men and 884 women had a mean age of 50 years, and more than one third were over 60 years of age . An overwhelming majority had at least one accompanying systemic illness, and the condition of more than half the patients was only fair or poor at the onset of therapy . Ciprofloxacin was administered in a unit dose of either 200 mg (68 percent of the patients) or 300 mg (28 percent) by intravenous infusion, generally over 30 minutes every 12 hours, at a mean daily dosage of 456 mg . The duration of intravenous therapy ranged from one to 57 days, with a mean of seven days; over 1,000 patients were treated for more than five days . Adverse events considered probably or possibly related to intravenous ciprofloxacin were reported in 15.8 percent of the courses; therapy was discontinued prematurely in 3 percent . Local reactions at the site of infusion were the most common, occurring in 4.4 percent of the courses . Changes in blood chemistry values (4.1 percent) included increases in alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase . Reports of adverse effects referable to the gastrointestinal tract (3.0 percent) were primarily nausea and diarrhea . Central nervous system reactions (1.8 percent) included convulsive seizures, headache, and dizziness . In comparative trials, events considered probably or possibly drug related were reported for 17.3 and 13.6 percent of the ciprofloxacin- and ceftazidime-treated patients, respectively . The incidence of adverse events other than local reactions at the infusion site was not significantly different between the ciprofloxacin- and ceftazidime-treated patients (12.7 percent versus 11.0 percent, p greater than 0.2).

Am J Med, 1989 Nov 30, 87(5A), 76S - 81S
Drug-drug interactions with ciprofloxacin and other fluoroquinolones; Polk RE; Early investigational trials with new quinolone antibiotics revealed two important drug-drug interactions: decreased fluoroquinolone absorption when co-administered with magnesium-aluminum antacids and inhibition of theophylline metabolism . Subsequent studies have investigated the mechanisms of these interactions . With respect to the effect of antacids, the absorption of all quinolones appears to be significantly reduced by antacids containing magnesium and/or aluminum, and concomitant administration must be avoided . Other cations, such as calcium, iron, and probably zinc, appear to interact in a similar manner . Chelation between the quinolone and cation is the most likely mechanism . With respect to the effect on theophylline metabolism, quinolones inhibit specific cytochrome P-450 isozymes responsible for metabolism of methylxanthines, although there are major differences between the quinolones . Enoxacin is the most potent inhibitor, followed by ciprofloxacin, pefloxacin, norfloxacin, and ofloxacin . Caffeine metabolism is also inhibited, although the clinical significance is uncertain . Case reports describe renal failure associated with concomitant administration of cyclosporine and ciprofloxacin, although controlled trials have not demonstrated an interaction . Enoxacin has little effect on warfarin metabolism, suggesting that other quinolones may not affect warfarin disposition . Case reports of central nervous system toxicity from administration of nonsteroidal anti-inflammatory agents and quinolones need confirmation . Patients should be monitored closely when potential interacting agents are used; it is probable that not all interactions have been identified.

Am J Med, 1989 Nov 30, 87(5A), 116S - 118S
Randomized study of intravenous/oral ciprofloxacin versus ceftazidime in the treatment of hospital and nursing home patients with lower respiratory tract infections; Trenholme GM et al.; This study determined the efficacy of intravenous ciprofloxacin in the treatment of institutionalized patients with lower respiratory tract infections . Hospitalized adults with hospital/nursing home-acquired pneumonia were randomly assigned to receive either intravenous ciprofloxacin or ceftazidime . When deemed feasible, therapy was changed to oral ciprofloxacin for patients who received ciprofloxacin intravenously or to any alternative oral therapy for patients who received ceftazidime . All 23 patients who received ciprofloxacin had a favorable response versus 15 of 21 patients who received ceftazidime (p less than 0.025) . One patient with a favorable response to ceftazidime developed a superinfection and one patient had a relapse during subsequent alternative oral therapy . However, patients who received ceftazidime were more severely ill than those who received ciprofloxacin on the basis of APACHE II scores.

Am J Med, 1989 Nov 30, 87(5A), 107S - 112S
Comparison of ciprofloxacin with ampicillin in acute infectious exacerbations of chronic bronchitis . A double-blind crossover study; Chodosh S et al.; Two separate acute bacterial exacerbations of chronic bronchitis and/or asthma were treated in 22 patients in a double-blind crossover study . One course of treatment consisted of 750 mg of ciprofloxacin twice daily and the other of 500 mg of ampicillin four times a day; each drug was given for 14 days . Patients were observed initially, every three to four days during therapy, and weekly during the post-therapy period . Observations that were recorded included graded chest symptoms and physical findings, vital signs, hematologic parameters, and objective sputum measurements (daily volume, purulence, differential quantitative cytology, bacterial counts, and physical properties) . Both antibiotic regimens were effective in resolving these acute bacterial exacerbations . Paired t test analysis revealed that ciprofloxacin is as clinically effective as ampicillin in the treatment of acute bacterial exacerbations in chronic bronchial disease, and appears to be superior in clearing bacterial pathogens from the sputum.

Am J Med, 1989 Nov 30, 87(5A), 89S - 91S
Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations; Harder S et al.; The inhibitory effects of ciprofloxacin and other quinolone derivatives on the hepatic cytochrome P450-dependent metabolism of caffeine have been investigated in humans . In vivo studies involved an intraindividual comparison of the single-dose kinetics of caffeine before and during quinolone administration in 12 healthy men . Changes of enzymatic caffeine degradation by the quinolones were studied in vitro using human liver microsomes from three donors . Enoxacin and pipemidic acid markedly prolonged caffeine elimination in vivo . A positive correlation exists between the doses of enoxacin or ciprofloxacin and the prolongation (increases) in the caffeine elimination half-life . Decreases in caffeine elimination, using doses of ciprofloxacin in the upper part of the recommended dose range, were approximately 1.5-fold in comparison with untreated control subjects, whereas in the case of enoxacin there was a sixfold change . In vitro results with enoxacin, ofloxacin, ciprofloxacin, and pipemidic acid show a competitive inhibition (Dixon plots) of caffeine 3-demethylation . Ciprofloxacin and enoxacin showed the strongest inhibitory effects in vitro, whereas ofloxacin had the lowest inhibitory effect . These results are qualitatively reflected in the in vivo results; however, the clinical effects may be dependent on pharmacokinetic disposition of the quinolone and this could explain the weak inhibitory action of ciprofloxacin in vivo.

Am J Med, 1989 Nov 30, 87(5A), 82S - 85S
Cyclosporine (cyclosporin A) pharmacokinetics in renal transplant patients receiving ciprofloxacin; Lang J et al.; The effects of ciprofloxacin administration on the pharmacokinetic parameters and biologic tolerance of cyclosporine (cyclosporin A) were determined in primary renal transplant patients . This study was performed in 10 patients (four women and six men) ranging in age from 26 to 64 years and body weight ranging from 46 to 88 kg . Ciprofloxacin therapy was started eight to 48 days (mean, 21 days) after transplantation, whereas the cyclosporine therapy was administered for seven to 48 days (mean, 18 days) post-transplant . Both ciprofloxacin and cyclosporine were administered every 12 hours . The mean cyclosporine dosage was 2.4 mg/kg per day, adjusted to obtain blood concentrations within the recommended range (i.e., 100 to 200 ng/ml) . The ciprofloxacin dosage was 750 mg orally twice daily for all patients . A pharmacokinetic study of cyclosporine was performed in each patient the day before starting ciprofloxacin treatment and after the 13th ciprofloxacin administration (i.e., Day 7 of ciprofloxacin therapy) . Cyclosporine concentrations were measured in whole blood by a specific high-performance liquid chromatography method and the following parameters were determined: minimal and maximal blood concentrations, area under the curve from zero to 12 hours, total body oral clearance, mean residence time, and elimination half life . Concurrently administered medications and serum creatinine values were recorded . No statistically significant difference was noted between the cyclosporine pharmacokinetic parameters before and during ciprofloxacin treatment . Serum creatinine levels were increased in four of 10 patients, but the increase was not considered related to ciprofloxacin treatment . In conclusion, it appears that ciprofloxacin can be administered to renal transplant patients without risk of interacting cyclosporine or enhancement of cyclosporine nephrotoxicity . Additional cyclosporine blood level monitoring is not particularly valuable in this setting.

Am J Med, 1989 Nov 30, 87(5A), 49S - 51S
Pharmacokinetics of three newer quinolones in pregnant and lactating women; Giamarellou H et al.; Sixty pregnant women with fetuses affected by beta-thalassemia major underwent termination of gestation induced by amniocentesis and intrauterine instillation of prostaglandin F2 alpha between 19 and 25 weeks . Pharmacokinetics of ciprofloxacin in maternal blood and amniotic fluid were studied after two doses of ciprofloxacin (200 mg intravenously every 12 hours), after two doses of pefloxacin (400 mg intravenously every 12 hours), and after two doses of ofloxacin (400 mg intravenously every 12 hours) . Twenty patients were studied in each group . The ranges of mean maternal serum and amniotic fluid levels were as follows: ciprofloxacin in maternal serum 0.01 to 0.28 micrograms/ml, in amniotic fluid 0.1 to 0.13 micrograms/ml; pefloxacin in maternal serum 2.65 to 4.31 micrograms/ml, in amniotic fluid 1.97 to 2.74 micrograms/ml; and ofloxacin in maternal serum 0.07 to 0.68 micrograms/ml, in amniotic fluid 0.13 to 0.25 micrograms/ml . Three groups of lactating women (10 women in each), were given three doses of 750 mg ciprofloxacin orally, 400 mg pefloxacin orally, and 400 mg ofloxacin orally . Serum and milk samples were obtained simultaneously at two, four, six, nine, 12, and 24 hours after dosage administration . The mean breast milk levels of ciprofloxacin at the corresponding time intervals were 3.79, 2.26, 0.86, 0.51, 0.20, and 0.02 micrograms/ml . The mean breast milk levels of pefloxacin were 3.54, 3.43, 2.93, 2.24, 1.79, and 0.88 micrograms/ml, and of ofloxacin, 2.41, 1.91, 1.25, 0.64, 0.29, and 0.05 micrograms/ml . It is concluded that all studied quinolones penetrate the placenta and are found in amniotic fluid at low concentrations and at much higher levels in breast milk . Because of the potential for quinolones to cause arthropathy in juvenile animals, their use should be avoided in pregnant and lactating women.

Am J Med, 1989 Nov 30, 87(5A), 40S - 45S
Ciprofloxacin intravenous dose variance; Lode H et al.; Following different intravenous dosages of ciprofloxacin in volunteers, only limited variation in serum concentrations have been reported using volunteers in both single- and multiple-dose studies . In patients, a greater variability in serum concentrations was reported during intravenous ciprofloxacin treatment . This was also the case in patients with varying degrees of renal insufficiency . However, no report exists of nonmeasurable ciprofloxacin serum concentrations during intravenous treatment in patients.

Am J Med, 1989 Nov 30, 87(5A), 37S - 39S
Ciprofloxacin: toxicologic evaluation of additional safety data; Schluter G; Long-term ciprofloxacin toxicology studies, additional data on arthorpathogenic effects, embryotoxicity studies in monkeys, and further results on central nervous system/interaction toxicology are presented . In the long-term studies of rats and mice, ciprofloxacin was given as food admixture in concentrations up to 5,000 ppm for 24 and 21 months, respectively . This treatment regimen did not result in any systemic toxicity and also did not give any indication of a tumorigenic effect of ciprofloxacin . In a study of juvenile dogs to investigate development of arthropathogenic lesions using magnetic resonance imaging techniques, an increase in width of the recessus suprapatellaris occurred only in those dogs in which marginal effects developed . Thus, this technique may be a suitable method to monitor juvenile patients receiving ciprofloxacin . Ciprofloxacin was also studied for its potential to act as an abortifacient when given orally or parenterally to cynomolgus monkeys . The data obtained did not give any indication of teratogenicity or embryolethality, and mean patterns of progesterone were similar between routes of administration, dose groups, and controls . Finally, data are presented that demonstrate that central nervous system interaction toxicity between quinolones and nonsteroidal anti-inflammatory drugs can be observed in rats only at therapeutically irrelevant high dose levels.

Am J Med, 1989 Nov 30, 87(5A), 148S - 151S
Comparison of parenteral ciprofloxacin with clindamycin-gentamicin in the treatment of pelvic infection; Apuzzio JJ et al.; A prospective, randomized study of intravenous followed by oral ciprofloxacin compared with the combination of intravenous clindamycin and gentamicin was conducted in 122 women hospitalized with pelvic infections . Clinical diagnoses included endometritis (97 patients) and uncomplicated pelvic inflammatory disease (25 patients) . Treatment successes for endometritis included 42 of 50 (84 percent) patients treated with ciprofloxacin compared with 35 of 47 (75 percent) treated with the clindamycin-gentamicin combination . Treatment successes for acute salpingitis included 10 of 10 (100 percent) treated with ciprofloxacin and 13 of 15 (87 percent) treated with clindamycin-gentamicin . Ciprofloxacin successfully eradicated Chlamydia trachomatis in 11 of 12 patients as did clindamycin-gentamicin in six of seven patients . In this study of pelvic infection, ciprofloxacin demonstrated efficacy comparable with the combination of clindamycin and gentamicin, and is effective against C . trachomatis.

Antimicrob Agents Chemother, 1989 Nov, 33(11), 1875 - 7
Effects of ciprofloxacin on testosterone and cortisol concentrations in healthy males; Waite NM et al.; Several inhibitors of oxidative drug metabolism inhibit the synthesis of endogenous compounds such as testosterone and cortisol . Since ciprofloxacin is a potent inhibitor of the metabolism of a number of drugs, we studied its effect on serum testosterone and cortisol concentrations in eight healthy male subjects . Blood samples were collected over a 12-h period under baseline conditions and following the first and final doses of ciprofloxacin (500 mg orally every 12 h for 4 days) . No significant differences in concentrations or area under the concentration-time curve were found when baseline values were compared with those observed for either testosterone or cortisol after ciprofloxacin administration . These results suggest that ciprofloxacin is unlikely to have either antiandrogenic side effects or clinical utility in lowering testosterone or cortisol concentration.

HPB Surg, 1989 Nov, 1(4), 319 - 26; discussion 326-7
The pharmacokinetics of the biliary excretion of ciprofloxacin; Ball CS et al.; The pharmacokinetics of ciprofloxacin excretion have been studied in 54 patients undergoing biliary and pancreatic operations with and without obstruction of the common bile duct . High concentrations were achieved in common duct bile within 20 minutes of intravenous injection and persisted for over 3 hours after 100 mg and for over 8 hours after 200 mg . The concentration of ciprofloxacin in the bile of functioning gall bladders was much greater than that in the common duct bile . Remarkably, it was identified in therapeutic concentrations in the bile of obstructed ducts . This and the rapid fall from initially high venous concentrations probably reflect diffusion from the circulation as a result of the exceptional tissue penetration . A unique feature of this study was the finding of clinically significant concentrations in the bile of obstructed ducts . Two patients developed wound infection and no side effects were observed . The broad spectrum antibiotic ciprofloxacin has potential as a useful agent for prophylaxis in biliary surgery maintaining biliary and venous concentrations in excess of the MIC90 for most biliary pathogens for more than 8 hours.

Antimicrob Agents Chemother, 1989 Oct, 33(10), 1704 - 8
Structure-epileptogenicity relationship of quinolones with special reference to their interaction with gamma-aminobutyric acid receptor sites; Akahane K et al.; The relationship between the chemical structure and epileptogenic activity of quinolones was investigated . When the quinolones were administered intravenously to mice concomitantly with oral biphenylacetic acid, a major metabolite of the nonsteroidal antiinflammatory drug fenbufen, enoxacin, norfloxacin, ciprofloxacin, and pipemidic acid, which have an unsubstituted piperazine moiety at the 7 position of their parent nuclei, provoked clonic convulsions and subsequent death at doses of 6.25 mg/kg or more in a dose-dependent manner . AM-1091 and T-3262, which have an unsubstituted aminopyrrolidine moiety at their 7 positions, were less epileptogenic than the compounds listed above were . In contrast, ofloxacin, AT-4140, and nalidixic acid, which have piperazine substituted with methyl group(s) or no piperazine moiety at their 7 positions, never induced convulsions, even at doses of 100 mg/kg . Lomefloxacin, which has a 3-methyl piperazine, however, provoked convulsions at doses of 6.25 mg/kg or more . In the presence of biphenylacetic acid, all the test quinolones except nalidixic acid competitively inhibited {3H}muscimol binding to receptor sites for gamma-aminobutyric acid (GABA) in vitro . Nalidixic acid did not inhibit the binding at all, even at the highest concentration tested, i.e., 10(-4) M . The 50% inhibition doses for {3H}muscimol binding varied within 4 orders of magnitude or more, between 10(-8) to more than 10(-4) M for various compounds, and there was a close correlation between the epileptogenic activities of quinolones and their inhibitory potencies for {3H}muscimol binding to GABA receptor sites . These results indicate that the epileptogenic activity of quinolones possibly relates to the GABA-like structures of substituents at their 7 positions, which act as antagonists of GABA receptors.

Am Rev Respir Dis, 1989 Oct, 140(4), 987 - 9
Minimal inhibitory concentrations of rifabutin, ciprofloxacin, and ofloxacin against Mycobacterium tuberculosis isolated before treatment of patients in Taiwan; Chen CH et al.; Minimal inhibitory concentrations (MICs) of rifabutin, ciprofloxacin, and ofloxacin were determined for "wild" Mycobacterium tuberculosis strains, susceptible to all antituberculosis drugs in the conventional test, isolated from newly diagnosed Taiwanese patients who had never had prior treatment for tuberculosis . These MICs were within the limits previously reported for strains isolated in the United States . The range of MICs of rifabutin for Taiwanese strains was 0.015 to 0.125 micrograms/ml; ciprofloxacin, 0.25 to 2.0 micrograms/ml; ofloxacin, 0.5 to 2.0 micrograms/ml . On the basis of an evaluation of the highest broth-determined MICs found in this and in a previous study, we suggest that the following MICs, when determined in 7H12 broth radiometrically, should be used as breakpoints to classify the strain as "susceptible": for rifabutin, 0.125 micrograms/ml or less; for ofloxacin and ciprofloxacin, 2.0 micrograms/ml or less.

Farmakol Toksikol, 1989 Sep-Oct, 52(5), 33 - 6
{The influence of ciprofloxacin and pefloxacin on blood coagulation and the anticoagulant effect of heparin}; Lepakhin VK et al.; At a single intravenous administration to rabbits ciprofloxacin (10 and 20 mg/kg) and pefloxacin (40 mg/kg) increased the blood coagulability . Administered in a dose of 20 mg/kg pefloxacin exerted no effect on the parameter . Ciprofloxacin (20 mg/kg) and pefloxacin (40 mg/kg) decreased the anticoagulant effect of heparin (100 U/kg).

J Chromatogr, 1989 Sep 1, 493(2), 337 - 46
High-performance liquid chromatographic method for the simultaneous determination of enrofloxacin and its primary metabolite ciprofloxacin in canine serum and prostatic tissue; Tyczkowska K et al.; A simple and sensitive high-performance liquid chromatographic method was developed for the determination of enrofloxacin and ciprofloxacin in canine serum and prostatic tissue . Sample preparation consisted of mixing canine serum with a 1:1 dilution of acetonitrile and 0.1 M sodium hydroxide followed by ultrafiltration through a 10,000 molecular mass cut-off filter . Prostatic tissue was sonicated with the same solution prior to ultrafiltration . Separation of these two quinolones in the ultrafiltrate was accomplished by ion-paired liquid chromatography using a reversed-phase analytical column eluted with an acetonitrile-methanol-water solution . Enrofloxacin and ciprofloxacin were detected by a photometric ultraviolet-visible detector set at 278.6 nm and confirmed by a photodiode array detector operating from 230 to 360 nm . The limits of detection for enrofloxacin and ciprofloxacin were 4 and 2 ng/ml, respectively.

Pharm Weekbl Sci, 1989 Aug 25, 11(4), 121 - 3
Two different dosages of ciprofloxacin in patients with respiratory tract infections; Brutel de la Riviere T et al.; Fifty-one patients with chronic obstructive lung disease with a proven bacterial respiratory tract infection were treated with ciprofloxacin 500 mg twice daily or 750 mg twice daily . Both dosages were given orally for approximately 10 days . The higher dosage showed a reduced amount of reinfections and relapses (19% and 16% versus 5% and 0%) . The overall results were the same in both groups . Adverse reactions were mild: nausea and visual disturbances were seen in five patients . Eight patients had slight liver test abnormalities . In one patient a seizure occurred . All adverse reactions were of a temporary nature.

J Antimicrob Chemother, 1989 Aug, 24(2), 209 - 13
The lack of long-term suppressive effect of ciprofloxacin on murine bone marrow; Somekh E et al.; In order to investigate the long-term effect of therapy with ciprofloxacin on haemopoietic cells, we administered ciprofloxacin orally in a daily dosage of 150 mg/kg/day in three divided doses for 11 days to syngeneic mice . A control group of mice was treated with saline . On the second, sixth, tenth and sixteenth day of ciprofloxacin therapy complete blood counts (cbc) and determination of haemopoietic progenitor cells (cfu-gm) from the tibial and femoral bone marrow were performed and followed by the transplantation of the bone marrow into lethally irradiated syngeneic mice . Bone marrow engraftment was evaluated ten days following transplantation by counting the visible colonies formed on the spleen surface (cfu-s) and by measuring the incorporation of 125I by the spleen and by the femurs of the transplanted mice . The results revealed that there was no statistical significance between the control and the ciprofloxacin treated mice in cbc, cfu-gm and cfu-s parameters . It is concluded that the suppressive effect of ciprofloxacin on haemopoietic cells appears only with very high concentrations of ciprofloxacin and is short-term and reversible.

Br J Clin Pharmacol, 1989 Aug, 28(2), 185 - 7
Co-administration of ciprofloxacin and cyclosporin: lack of evidence for a pharmacokinetic interaction; Tan KK et al.; Ciprofloxacin is widely reported to lower theophylline clearance in patients . Since cyclosporin and theophylline are metabolized by cytochrome P-450 enzymes in the human liver, we investigated whether ciprofloxacin could alter the pharmacokinetics of cyclosporin in healthy volunteers . There was no significant difference (P greater than 0.05) in the pharmacokinetic parameters estimated for cyclosporin without and during ciprofloxacin administration . The results of the present study suggest that ciprofloxacin is unlikely to affect the pharmacokinetics of cyclosporin to a clinically important extent at a dosage of 500 mg twice a day.

Rev Infect Dis, 1989 Jul-Aug, 11 Suppl 5, S1102 - 6
Pharmacokinetics of fluorinated 4-quinolones in the aged; Norrby SR et al.; Differences between the pharmacokinetics of the new fluoroquinolones in the young and in the elderly have been demonstrated for ciprofloxacin, enoxacin, norfloxacin, and ofloxacin . Comparative studies of the young and the elderly are still lacking for pefloxacin . With ofloxacin and norfloxacin, the age-related pharmacokinetic differences seem for the most part to be due to differences in the renal handling of the drugs . With ciprofloxacin and enoxacin more profound differences have been reported . The peak concentrations of ciprofloxacin and enoxacin in serum increase with age, without a concurrent increase in serum half-life . This cannot be explained by differences in the distribution of the drug or by reduced metabolism . The most probable explanation for the age-related differences in the disposition of ciprofloxacin is a more efficient absorption of the drug in the elderly . With enoxacin, an increase in the nonrenal clearance of the drug with age has been demonstrated . The clinical consequence of the age-related differences in the pharmacokinetics of ciprofloxacin and enoxacin is that these antibiotics should be administered at lower doses to the elderly.

Rev Infect Dis, 1989 Jul-Aug, 11 Suppl 5, S1382 - 9
New quinolones: in vitro effects as a potential source of clinical toxicity; Forsgren A et al.; 4-Quinolones affect mammalian cellular functions in vitro in several ways . High concentrations inhibit DNA replication, but individual genes are perhaps sensitive to lower concentrations of drug . Inhibition of cell proliferation differs widely among 4-quinolones . Ciprofloxacin and norfloxacin are the most antiproliferative, inhibiting cell growth by approximately 30% at 20 mg/L . Genotoxicity tests with 4-quinolones are probably "false-positive" as a result of increased {3H}thymidine uptake that is not related to DNA damage . Ciprofloxacin at greater than or equal to 10 mg/L causes significant strand breaks in DNA, which seemingly are quickly repaired and do not cause mutations or cancer . Production of immunoglobulin is inhibited by ciprofloxacin at a concentration of 5 mg/L, but production of the growth factor interleukin 2 (IL-2) is increased by 4-quinolones at the same concentration and is hyperinduced at higher concentrations . Thus the effects are very contradictory . Increased production of IL-2 may contribute to central nervous system adverse effects . 4-Quinolones in combination with theophylline or antiinflammatory drugs may inhibit gamma-aminobutyric acid receptor binding and thereby have adverse effects on the central nervous system . Some 4-quinolones induce crystalluria, which may be nephropathic.

Antimicrob Agents Chemother, 1989 Jul, 33(7), 1118 - 20
Relative bioavailability in healthy volunteers of ciprofloxacin administered through a nasogastric tube with and without enteral feeding; Yuk JH et al.; The bioavailability of ciprofloxacin after its administration through a nasogastric (NG) feeding tube was studied in six healthy volunteers . Each subject received, on separate occasions, an intact 750-mg ciprofloxacin tablet, a crushed tablet as a suspension through an NG tube, and a crushed tablet as a suspension through an NG tube while receiving enteral feeding . No statistically significant differences were observed in the area under the curve, maximum concentration in serum, and time to peak concentration among these three modes of administration . These findings suggest that ciprofloxacin is well absorbed after administration via an NG tube (compared with an orally administered intact tablet) even in the presence of enteral feeding.

Clin Pharmacol Ther, 1989 Jun, 45(6), 608 - 16
The effect of cirrhosis on the steady-state pharmacokinetics of oral ciprofloxacin; Frost RW et al.; The pharmacokinetics of ciprofloxacin, a carboxyquinolone, was studied after oral administration of the drug to seven patients with biopsy-proved cirrhosis and to seven healthy volunteers . Serum concentrations of ciprofloxacin and its three metabolites--desethylene ciprofloxacin (M1), sulfociprofloxacin (M2), and oxociprofloxacin (M3)--were measured by an HPLC procedure . The pharmacokinetic parameters for ciprofloxacin were not significantly altered in cirrhotic patients . The elimination half-life (t 1/2) and the area under the serum concentration versus time curve (AUC) were, respectively, 3.71 hours and 16.18 microgram.ml-1.hr-1 in the normal subjects and 3.47 hours and 18.38 micrograms.ml-1.hr-1 in patients with cirrhosis . The formation of oxociprofloxacin was reduced by approximately one half in the cirrhotic subjects, as the Cmax was 0.29 micrograms/ml in normal subjects versus 0.14 micrograms/ml in cirrhotic patients and the mean AUC(0-t) was 1.54 micrograms.ml-1.hr-1 in normal subjects versus 0.70 micrograms.ml-1.hr-1 in cirrhotic patients . However, there appeared to be no significant difference between groups with respect to desethylene ciprofloxacin and sulfociprofloxacin . Therefore it appears from this study that no dosage adjustment is required in patients with hepatic cirrhosis.

Antimicrob Agents Chemother, 1989 Jun, 33(6), 987 - 8
Randomized double-blind evaluation of ciprofloxacin and doxycycline for Mediterranean spotted fever; Gudiol F et al.; A study of 43 patients with Mediterranean spotted fever showed that a 2-day course of ciprofloxacin or a 2-day course of doxycycline may be an effective mode of therapy . All patients in both arms of the study were cured; however, doxycycline produced a more rapid defervescence.

Eur J Clin Microbiol Infect Dis, 1989 Jun, 8(6), 515 - 20
Pharmacokinetics of ciprofloxacin in the elderly: increased oral bioavailability and reduced renal clearance; Ljungberg B et al.; The pharmacokinetics of ciprofloxacin was studied after single intravenous and oral doses of 250 mg and during and after a five-day oral regimen of 500 mg twice daily in eight young (22-34 years) and eight elderly (63-76 years), healthy male volunteers . The absolute bioavailability of an oral dose was greater in the elderly than in the young subjects at both 250 mg (72 versus 58%; p less than 0.05) and 500 mg (79 versus 63%; p less than 0.05) . Distribution was unaffected by age . The physiological aging of the kidneys resulted in a reduced renal clearance, while no significant changes in non-renal clearance, total clearance and terminal half-life were found in the elderly . The age-related increase in the bioavailability of ciprofloxacin, whether due to facilitated absorption and/or reduced first-pass elimination, is a hitherto unique finding for antibiotics . As a consequence, reduction of orally administered doses of ciprofloxacin should be considered for elderly patients.

Pathol Biol (Paris), 1989 May, 37(5), 346 - 9
{In vitro determination of the sensitivity of mycobacteria to fluoroquinolones}; Dailloux M et al.; In vitro activity of four fluorinated quinolones: pefloxacin, norfloxacin, ciprofloxacin, ofloxacin were determined against various clinical isolates of mycobacteria . The method of agar dilution was used, seventy strains of ten species were tested: Mycobacterium tuberculosis (25), Mycobacterium bovis (5), Mycobacterium africanum (2), BCG (5), Mycobacterium kansasii (6), Mycobacterium marinum (5), Mycobacterium avium (11), Mycobacterium xenopi (6), Mycobacterium chelonae (3), Mycobacterium fortuitum (2) . Except for Mycobacterium avium and Mycobacterium chelonae (CMI 100% greater than 8 mg/l) fluorinated quinolones showed activity against tested mycobacteria (CMI 100% less than or equal to 8 mg/l) . Ofloxacin and ciprofloxacin where found to be the most active . Their activity against the different strains of Mycobacterium tuberculosis was unrelated to their susceptibility or resistance to the antituberculous drugs.

Antimicrob Agents Chemother, 1989 May, 33(5), 788 - 9
Efficacy of ciprofloxacin against Leptospira interrogans serogroup icterohaemorrhagiae; Shalit I et al.; Ciprofloxacin activity against Leptospira interrogans serogroup icterohaemorrhagiae was studied in vitro and in an animal model . The MBC of ciprofloxacin was 0.6 microgram/ml . Three of three Syrian hamsters died 8 to 9 days after intraperitoneal challenge with 10(6) leptospires . In contrast, five of six animals given ciprofloxacin 3 or 5 days after challenge survived.

J Antimicrob Chemother, 1989 May, 23(5), 789 - 91
Open study of ciprofloxacin in enteric fever; Stanley PJ et al.; Thirty adult patients with typhoid or paratyphoid fever were treated with ciprofloxacin . All patients were cured with eradication of the causative organism . No major adverse reactions were seen . Ciprofloxacin is an effective agent for the treatment of enteric fever.

J Antimicrob Chemother, 1989 Apr, 23(4), 597 - 604
Rapid HPLC assay of fluoroquinolones in clinical specimens; Chan CY et al.; A simple isocratic HPLC procedure was developed for the analysis of seven quinolones and their metabolites in clinical specimens . It is likely that this system can be used for the assay of many other quinolone compounds, but not for nalidixic acid and the ciprofloxacin metabolite sulpho-ciprofloxacin which appear to be adsorbed in the column . Sample preparation takes approximately 20 min, and HPLC analysis is completed within 15 min with a simple solvent system eluted on a reversed phase column . The procedure is rapid, sensitive and specific, and is a modification of an assay for chloramphenicol and beta-lactam antibiotics . This method is therefore particularly useful for clinical laboratories, since a single HPLC system can be used for assays of chloramphenicol, beta-lactams and quinolones.

J Clin Chem Clin Biochem, 1989 Apr, 27(4), 232 - 3
Gyrase inhibitor ciprofloxacin in human parotid saliva; Adler D et al.; The excretion of ciprofloxacin (Ciprobay) via the human parotid gland was investigated . 2 h after an intravenous bolus injection (200 mg ciprofloxacin) mean serum concentrations of 0.43 mg/l were achieved, and these decreased within 6 h after injection to 0.17 mg/l . The concentrations of the gyrase inhibitor in parotid saliva showed a close positive correlation to the serum levels (r = 0.96), but they were significantly lower than serum levels . They decreased from 0.1 mg/l 2 h after injection to 0.04 mg/l after 6 h.

J Chemother, 1989 Apr, 1(2), 103 - 6
Use of oral ciprofloxacin in community-acquired pneumonia; Chrysanthopoulos CJ et al.; Twenty-five acutely ill patients, 21 men and 4 women aged 20-90 years (mean, 54 years) with acute community-acquired bacterial pneumonia, were treated with ciprofloxacin orally . The diagnosis of pneumonia was based on clinical and roentgenographic evidence of pulmonary infiltrate and a Gram stain of sputum demonstrating neutrophils and bacteria . Initially, 12 patients received 750 mg of ciprofloxacin orally every 12 hours for 3-6 days (mean, 3.8 days) followed by 500 mg of oral medication twice daily for 4-7 days (mean, 4.8 days) . The remaining 13 patients received 500 mg of ciprofloxacin orally for 8-15 days (mean, 8.5 days) . Treatment was successful in all patients (100%) . No superinfections occurred, and there was no development of resistance . The drug was well tolerated and only moderate transient elevation of transaminase levels (serum glutamic-oxaloacetic transaminase and serum glutamine pyruvic transaminase) was noted in one patient.

Antimicrob Agents Chemother, 1989 Apr, 33(4), 589 - 90
Enhanced elimination of ciprofloxacin after multiple-dose administration of rifampin to rabbits; Barriere SL et al.; The combination of ciprofloxacin and rifampin is potentially useful for the treatment of selected infections . However, rifampin may induce the metabolism of ciprofloxacin . Ciprofloxacin was given in single doses to healthy rabbits before and after six daily doses of intramuscular rifampin . Total clearance of ciprofloxacin increased from 0.96 +/- 0.32 (standard deviation) to 1.57 +/- 0.63 liters/h per kg (P less than 0.05) . This change in elimination is potentially significant for the outcome of experimental infections in rabbits.

Infection, 1989 Mar-Apr, 17(2), 88 - 9
Mycobacterium kansasii and Pneumocystis carinii pneumonia in a patient with the acquired immunodeficiency syndrome; Vurma-Rapp U et al.; The case of a Swiss AIDS patient suffering from Mycobacterium kansasii lung disease is described . The course of the illness was complicated by Pneumocystis carinii pneumonia . Therapy with isoniazid, ethambutol, clofazimine, ciprofloxacin and, after the onset of P . carinii pneumonia, trimethoprim-sulfamethoxazole led to a rapid and sustained clinical recovery of the patient.

Postgrad Med J, 1989 Mar, 65(761), 190 - 1
Treatment of multiple subcutaneous Nocardia asteroides abscesses with ciprofloxacin and doxycycline; Bath PM et al.; We report on the successful use of oral ciprofloxacin and doxycycline in the treatment of multiple subcutaneous nocardial abscesses in an immunocompromised patient with active non-Hodgkin's lymphoma . This relatively inexpensive regimen allowed the patient to return home and was not associated with any significant side effects . The patient has shown no sign of relapse of her nocardial infection over an 8-month period on the above regimen.

J Foot Surg, 1989 Mar-Apr, 28(2), 100 - 5
Ciprofloxacin for the treatment of osteomyelitis: a review; Hessen MT et al.; The authors review the use of ciprofloxacin, a new oral quinolone antibiotic, for the treatment of bone infections . The article discusses the spectrum of activity, pharmacokinetics, and toxicity of the quinolone agents . The authors also provide a detailed discussion of the efficacy of ciprofloxacin for osteomyelitis in animal studies and human trials.

Antimicrob Agents Chemother, 1989 Mar, 33(3), 283 - 90
Mechanisms of quinolone resistance in Escherichia coli: characterization of nfxB and cfxB, two mutant resistance loci decreasing norfloxacin accumulation; Hooper DC et al.; Two genetic loci selected for norfloxacin (nfxB) and ciprofloxacin (cfxB) resistance were characterized . Both mutations have previously been shown to confer pleiotropic resistance to quinolones, chloramphenicol, and tetracycline and to decrease expression of porin outer-membrane protein OmpF . nfxB was shown to map at about 19 min and thus to be genetically distinct from ompF (21 min), and cfxB was shown to be very closely linked to marA (34 min) . cfxB was dominant over cfxB+ in merodiploids, in contrast to other quinolone resistance mutations . The two loci appear to interact functionally, because nfxB was not expressed in the presence of marA::Tn5 . Both nfxB and cfxB decreased the expression of ompF up to 50-fold at the posttranscriptional level as determined in strains containing ompF-lacZ operon and protein fusions . Both mutations also decreased norfloxacin accumulation in intact cells . This decrease in accumulation was abolished by energy inhibitors and by removal of the outer membrane . These findings, in conjunction with those of Cohen et al . (S . P . Cohen, D . C . Hooper, J . S . Wolfson, K . S . Souza, L . M . McMurry, and S . B . Levy, Antimicrob . Agents Chemother . 32:1187-1191, 1988), suggest a model for quinolone resistance by decreased permeation in which decreased diffusion through porin channels in the outer membrane interacts with a saturable drug efflux system at the inner membrane.

J Antimicrob Chemother, 1989 Feb, 23(2), 253 - 9
Pharmacokinetics of intraperitoneal ciprofloxacin in patients on CAPD; Dharmasena D et al.; The concentration of ciprofloxacin was assayed in plasma and peritoneal dialysate following intraperitoneal administration of the drug in the absence of bacterial peritonitis . After administration of a single dose of 5 mg/kg, ciprofloxacin was rapidly absorbed, producing a peak plasma concentration of 1.9 +/- 0.6 mg/l after 3-4 h with an apparent bioavailability of 0.84 . In a separate study, following the administration of 25 mg/l for eight consecutive CAPD cycles the intraperitoneal concentration of ciprofloxacin fell to a mean of 8.4 +/- 4.6 mg/l after 4 h cycles and to a mean of 3.0 +/- 3.2 mg/l after 12 h cycles . During the period of administration the mean plasma concentration was 0.5 +/- 0.2 mg/l . Analysis of dialysate for 48 h after cessation of drug administration demonstrated ciprofloxacin to be present in effluent from only two of the six patients, confirming its poor peritoneal elimination.

J Chemother, 1989 Feb, 1(1), 30 - 4
Ciprofloxacin versus ceftazidime in skin and soft tissue infections; Thadepalli H et al.; Intravenous ciprofloxacin therapy was evaluated in comparison with i.v . ceftazidime in the treatment of skin and soft tissue infections and were found to be comparable . Intravenous or peroral forms of ciprofloxacin may be used instead of intravenously given third generation cephalosporins or aminoglycosides in the treatment of even severe infections of the skin and soft tissue.

J Antimicrob Chemother, 1989 Feb, 23(2), 247 - 51
The effect of ciprofloxacin and pefloxacin on bone marrow engraftment in the spleen of mice; Somekh E et al.; In order to investigate the in-vivo effect of ciprofloxacin and pefloxacin on bone marrow engraftment in mice, irradiated mice were transplanted with bone marrow graft (5 x 10(5) cells/mouse) obtained from syngeneic mice . Three groups of mice (30 mice in each) received a bone marrow graft incubated for 1 h with ciprofloxacin at concentrations of 0.5, 5 and 50 mg/l . Six additional groups (30 mice in each) were treated twice daily after transplantation with intra-peritoneal injections of ciprofloxacin in dosages of 25, 50 and 100 mg/kg/24 h or pefloxacin in dosages of 10 and 100 mg/kg/24 h . Evaluation of bone marrow engraftment was performed in animals injected with I125 Iodo-deoxyuridine (0.5 mu Ci/mouse) by radioactive counting of the entire spleen and also by counting visible colonies on the spleen surface . The results of this study demonstrate a statistically significant depression of bone marrow graft uptake (P less than 0.05, student t-test) in mice treated twice daily with ciprofloxacin in dosage of 100 mg/kg/24 h, a concentration far beyond the therapeutic range.

Br J Hosp Med, 1989 Jan, 41(1), 62, 66 - 7
Ciprofloxacin; Smyth EG et al.; Ciprofloxacin is a useful, orally available, non-toxic broad-spectrum antibiotic . Despite its novel mode of action, resistance is arising and we feel the drug should be reserved for specific indications where it can be of enormous value.

Scand J Infect Dis Suppl, 1989, 60, 35 - 8
Effect of ciprofloxacin compared to gentamicin in the treatment of experimental intraabdominal infections in rats; Lahnborg G et al.; A reproducible experimental model of intraabdominal infections in rats has been developed in order to stimulate intraabdominal sepsis in patients . Preoperatively, the rats were fed with lean ground beef for two weeks in order to change the intestinal flora to one similar to that of humans . A 1-cm segment of ileum was isolated on its vascular pedicle . The intestine was then divided at each end of the segment and intestinal continuity was re-established by an end-to-end anastomosis . The segment of ileum was then returned to the abdominal cavity . This experimental model was used to compare the efficacy of ciprofloxacin alone and in combination with clindamycin with the combination gentamicin and clindamycin in the treatment of intraabdominal infections . Eighty per cent of the untreated animals died within four days . Within six days, 30% of the animals receiving ciprofloxacin died . Animals treated with ciprofloxacin plus clindamycin or gentamicin plus clindamycin had a significantly decreased mortality and increased cure rates during the experimental period . Only 5% of these animals died . Thus the combination of ciprofloxacin and clindamycin seems to be as successful as gentamicin plus ciprofloxacin in the treatment of intraabdominal infections.

Scand J Infect Dis Suppl, 1989, 60, 28 - 34
Does ciprofloxacin affect the inner ear? A preliminary report; Bagger-Sjoback D et al.; Ciprofloxacin, a 4-quinolone antibiotic was tested regarding its possible influence on the inner ear sensory epithelia . Adult guinea pigs were injected intraperitoneally with ciprofloxacin in a dosage of 25, 50, 100 and 150 mg/kg body weight per day . The animals in the high dosage ranges stopped eating and consequently lost weight quite rapidly . After sacrifice, the inner ear sensory epithelia were removed for ultrastructural analysis . The general outline of the vestibular sensory epithelia as well as the cochleae were normal . Mild changes in the sensory hairs of the third row of cochlear outer hair cells were noted in the specimens obtained from the high dose animals . These changes were discrete and did not resemble any previously known pattern of ototoxic damage . At present no data indicate that ciprofloxacin has a toxic effect on the inner ear.

Scand J Infect Dis Suppl, 1989, 60, 23 - 7
Influence of age on the pharmacokinetics of ciprofloxacin; Nilsson-Ehle I et al.; Data from 4 previously published reports on kinetics after oral ciprofloxacin administration are reviewed . Preliminary results from a study with oral and intravenous administration in elderly and young, healthy males are presented . The total clearance of ciprofloxacin is maintained in the elderly, while the renal clearance is reduced as a consequence of the age-related, physiological reduction of kidney functions . After oral administration there is, furthermore, an increased AUC and Cmax, which are explained by a higher bioavailability of an oral dose in the elderly (72.4%) as compared to young volunteers (58.4%).

Ther Drug Monit, 1989, 11(4), 463 - 70
A high-performance liquid chromatographic method for the measurement of deferoxamine in body fluids; Tesoro A et al.; A high-performance liquid chromatography method for the analysis of deferoxamine (DFO) in 100 microliters of serum or plasma is described . The procedure involves the addition of the internal standard ciprofloxacin to the sample, followed by ultrafiltration to remove protein . The ultrafiltrate is then directly injected into the chromatography system . Separation is achieved using a reverse-phase mu Bondapak C18 column and a ternary solvent system (sodium phosphate:acetonitrile:methanol) running at 2.0 ml/min . Assay time is 10 min, and chromatograms show no interference from coadministered drugs during this period of time . Coefficients of variation were found to be less than 5%, and analytical recovery of DFO was 85% . Validation experiments in an experimental dog model and in patients with iron overload demonstrate that the method is appropriate for studying the pharmacokinetics of DFO in thalassemic patients receiving drug for the treatment of chronic iron overload.

Microbios, 1989, 58(235), 113 - 26
Ciprofloxacin concentrations in serum, bone and bone marrow of rabbits; Gill LR et al.; Ciprofloxacin concentrations were determined in serum, bone and bone marrow of rabbits . Four experimental groups of animals were examined: group A (n = 6) received a dosage of 60 mg/kg/day intramuscularly for 4 weeks, groups B (n = 6), C (n = 15) and D (n = 15) received dosages of 120 mg/kg/day subcutaneously for 2 days, 2 weeks, and 4 weeks, respectively . In the kinetic portion of the study, peak serum concentrations of ciprofloxacin measured at the 15 min sampling time were: 2.61 +/- 0.27 micrograms/ml in the 60 mg/kg/day group (group A) and 3.24 +/- 0.78 micrograms/ml in the 120 mg/kg/day group (group B) . At necropsy, rabbits in group A had mean ciprofloxacin concentrations of 3.60 +/- 2.27 micrograms/ml in serum, 2.24 +/- 1.19 micrograms/g in marrow and 1.19 +/- 0.44 micrograms/g in bone . Rabbits in group B achieved mean levels of 4.02 +/- 1.23 micrograms/ml in serum, 2.48 +/- 0.79 micrograms/g in marrow, and 1.35 +/- 0.40 micrograms/g in bone . Rabbits in group C achieved mean levels of 5.65 +/- 2.16 micrograms/ml in serum, 3.74 +/- 1.33 micrograms/g in marrow and 1.92 +/- 0.94 micrograms/g in bone . Rabbits in group D achieved mean levels of 7.24 +/- 2.50 micrograms/ml in serum, 4.48 +/- 1.68 micrograms/g in marrow, and 1.93 +/- 0.54 micrograms/g in bone . Differences between mean values for the four experimental groups were not statistically significant.

Int J Clin Pharmacol Res, 1989, 9(1), 37 - 41
Pharmacokinetics of ciprofloxacin in impaired liver function; Esposito S et al.; The pharmacokinetics of ciprofloxacin after a single 500 mg oral dose was studied in one group of healthy volunteers and in patients affected by liver cirrhosis and classified into three groups according to Child-Turcotte criteria . The serum concentrations were determined by an agar well diffusion assay 0.5, 1, 3, 6, 12 and 24 h after the administration of the drug . No significant differences were noticed in Cmax, Tmax, T1/2 and AUCtot in the group A and B of patients and in the control group . Class C patients showed on the other hand a Cmax 15-25% higher than in other groups (2.74 mcg/ml), a T1/2 1.12-1.42 hours longer than in other groups and a consequent much higher AUCtot (17.70 mcg/h/ml) . The concomitant administration of diuretics of anti-H2 drugs was also evaluated as possible factors affecting the ciprofloxacin pharmacokinetics, but no significant differences were noticed . A mild or moderate impairment of the liver function did not affect the pharmacokinetics of ciprofloxacin, but the severe impairment of the liver function could affect its Cmax and serum half-life, so that further studies with multiple doses will be needed to evaluate if any dosage adjustment would be required in these patients.

Int J Clin Pharmacol Res, 1989, 9(1), 29 - 35
Steady-state serum pharmacokinetics and bioequivalence of 500 mg oral versus 200 mg intravenous ciprofloxacin; Garraffo R et al.; The pharmacokinetics of ciprofloxacin were examined after five days of treatment with 500 mg orally and 200 mg intravenously twice a day, in six healthy volunteers in an open, randomized crossover study . The ciprofloxacin concentrations were determined in serum by high performance liquid chromatography . The mean serum peak concentrations were obtained in 1 to 1.5 h by the oral route and the values reached were similar after the oral and intravenous dose (2.56 +/- 0.62 micrograms/ml and 2.6 +/- 0.67 micrograms/ml respectively) . The terminal elimination half-life was about 4.5 h for oral form and 5 h for intravenous form . The absolute bioavailability of the oral ciprofloxacin was about 83%.

Sex Transm Dis, 1989 Jan-Mar, 16(1), 7 - 10
Clinical efficacy of new quinolones for therapy of nongonococcal urethritis; Perea EJ et al.; Ninety-five patients with nongonococcal urethritis were enrolled in a double-blind study and were randomly assigned to a one-week treatment with ciprofloxacin (500 mg twice daily) or ofloxacin (200 mg twice daily) . Two weeks after treatment the results obtained for the 79 evaluated patients were as follows: 59 patients (75%) were clinically cured, and of the 54 patients with initial positive cultures, 39 (72%) remained culture-negative . We did not find any statistically significant differences between the results obtained with the two treatments . These results did not vary with the cause . Patient compliance with the regimens of two doses per day was excellent, and no serious adverse effects occurred with either drug.

Scand J Infect Dis Suppl, 1989, 60, 39 - 45
Effect of ciprofloxacin on human lymphocytes--laboratory studies; Forsgren A et al.; 4-Quinolones affect mammalian cellular functions in vitro in several ways . Inhibition of cell proliferation differ widely among 4-quinolones . Ciprofloxacin is one of the most antiproliferative inhibiting cell growth with about 30% at 20 mg/l . Genotoxicity tests with 4-quinolones are probably "false" positive due to an increased {3H}-thymidine uptake not related to DNA damage . Ciprofloxacin at 10 mg/l and up causes significant DNA strand breaks which seemingly are quickly repaired and not causing mutations or cancerogenesis . Ciprofloxacin at 5 mg/l inhibits immunoglobulin production but the growth factor interleukin 2 (IL-2) is increased by 4-quinolones at the same concentration and hyperinduced at higher concentrations . Thus the effects are very contradictory . Increased IL-2 may contribute to CNS side effects.

Scand J Infect Dis Suppl, 1989, 60, 120 - 8
Safety of ciprofloxacin . A review; Rahm V et al.; In clinical trials phase II and III world wide 8,861 courses of ciprofloxacin were entered into the data base for safety evaluation . The following adverse reactions were observed-gastrointestinal 5%, metabolic and nutritional 4.6%, central nervous system 1.6%, skin 1.4%, hemic and lymphatic 1%, cardiovascular 0.4%, body as a whole 0.4%, urogenital 0.3%, special senses 0.3%, musculo-skeletal 0.1%, respiratory 0.08% . Total incidence of adverse reactions was 10.2% . Ciprofloxacin interacts with theophylline and certain antacids . Caution should be exercised in treating patients with known history of convulsions . Crystalluria does not appear to be a problem . Ciprofloxacin is well tolerated and side effects are usually mild or moderate in intensity . However, unusual and unexpected reactions have to be watched for.

Scand J Infect Dis Suppl, 1989, 60, 116 - 9
Tolerance of intravenous ciprofloxacin; Thorsteinsson SB et al.; Available information about the safety of intravenous (i.v.) administration of ciprofloxacin is reviewed . No increased incidence of systemic toxicity is apparent over the oral route . CNS side effects occur, but at a low rate and they are mild . Caution is indicated in patients with tendency for seizures . Laboratory changes are minimal, mainly mild elevations of liver enzymes . No increased risk of crystalluria has been seen . Local side effects in the form of erythema and burning are relatively common in some volunteer studies and are also seen in clinical studies, infusion phlebitis also occurs . It is recommended that i.v . ciprofloxacin is administered in slow infusion through a large or preferably central vein.

Clin Pharmacokinet, 1989, 16 Suppl 1, 52 - 8
Enoxacin absorption and elimination characteristics; Toothaker RD; Enoxacin, a new fluoroquinolone antibiotic, is rapidly and extensively absorbed after oral administration and has a bioavailability independent of dose and only slightly delayed by concurrent food . Plasma concentrations are similar for both intravenous and oral administration . The t1/2 for enoxacin ranges from 4 to 6 hours, which allows effective twice-daily administration without significant accumulation . Plasma enoxacin concentrations may be slightly higher in elderly subjects, but this change does not necessitate dosage adjustment in older patients with adequate renal function . Enoxacin and ciprofloxacin decrease the clearance of coadministered theophylline, whereas ofloxacin does not appear to greatly alter methylxanthine clearance . Maalox (a magnesium-aluminium hydroxide antacid) significantly decreases the oral bioavailability of ciprofloxacin, ofloxacin and enoxacin, and use of these agents with antacids should be avoided . Enoxacin is a highly effective oral anti-infective agent with excellent bioavailability characteristics, a relatively slow rate of elimination and simple, well-defined requirements for dosage modification in patients with renal dysfunction.

Enferm Infecc Microbiol Clin, 1989 Jan, 7(1), 12 - 7
{Clinical experience with a new fluoroquinolone: ciprofloxacin}; Azanza JR et al.; Twenty one adult patients, both males and females, with 32 bacterial infections of several localizations and moderate to severe prognosis were treated with ciprofloxacin (200 mg every 12 hours), initially intravenously and then with 500 mg every 12 hours orally during 25 +/- 11 days . At the end of the evolution period it was found that 28 infections (87.5%) were cured in 24 of the 28 patients (85.7%), in three patients there was a definite clinical improvement and the treatment failed in the remaining patient . Adverse reactions were suspected in 2 patients, but their relation with the administration of ciprofloxacin was considered to be remote . In 3 patients mild leukopenia without clinical relevance was detected.

Arch Surg, 1988 Dec, 123(12), 1487 - 90
A comparison of the penetration of two quinolones into intra-abdominal abscess; Tudor RG et al.; A low-mortality model of an intra-abdominal abscess in the rat has been used to study the penetration of two quinolone agents into pus . Maximum concentrations in pus after intravenous injections were achieved at four hours (ciprofloxacin: 12.7 +/- 3.69 mg/L, fleroxacin: 2.25 +/- 1.82 mg/L), whereas fleroxacin given orally reached the maximum level at two hours (13.39 +/- 3.13 mg/L) . Higher concentrations of fleroxacin were recorded in pus than in serum at each time point up to eight hours after administration, but pus levels of ciprofloxacin only exceeded serum levels after 1.5 hours . These antibiotics appear to have a unique property of high penetration into established abscesses and may have an important therapeutic role in the treatment of patients with multiple interloop abscesses.

Antimicrob Agents Chemother, 1988 Nov, 32(11), 1735 - 7
In vitro activities of ofloxacin and four other new quinoline-carboxylic acids against Chlamydia trachomatis; Nagayama A et al.; The in vitro activities of five new quinoline-carboxylic acids against 2 reference strains and 45 clinical isolates of Chlamydia trachomatis of genital origin were compared with the activities of minocycline and doxycycline . Ofloxacin was the third most active agent (after the two tetracyclines), followed by ciprofloxacin, NY-198, and AM-833.

Antimicrob Agents Chemother, 1988 Nov, 32(11), 1624 - 6
Quinolones, theophylline, and diclofenac interactions with the gamma-aminobutyric acid receptor; Segev S et al.; Epileptic seizures and hallucinations, which are rare in patients receiving quinolones, have been observed more frequently in patients receiving both quinolones and either theophylline or nonsteroidal anti-inflammatory drugs . Inhibition of gamma-aminobutyric acid (GABA) binding to the GABA receptor, resulting in general excitation of the central nervous system, may be the underlying mechanism of these adverse phenomena . We demonstrate here that ciprofloxacin displaced a GABA-like substance (muscimol) from the GABA receptor when administered in concentrations of greater than 10(-4) M . These concentrations were lower than those needed by pefloxacin, ofloxacin, and nalidixic acid to reach a concentration that inhibits 50% of binding . The combination of ciprofloxacin and theophylline was additive in reducing the level of muscimol binding to the GABA receptor, whereas a diclofenac-ciprofloxacin combination had no effect . The concentrations of both ciprofloxacin and the other quinolones used were much higher than those observed in human serum and cerebrospinal fluid in a clinical setting; however, different human GABA receptor affinities, preexisting GABA excitation, or underlying central nervous system disease may amplify the excitatory side effects observed by the co-administration of quinolones and theophylline . Attention should be paid to the possible epileptogenic activity of the simultaneous administration of quinolones with aminophylline, nonsteroidal anti-inflammatory drugs, or other unpredictable drugs.

J Antimicrob Chemother, 1988 Oct, 22(4), 499 - 504
Penetration of ciprofloxacin in bronchial secretions after intravenous administration; Berre J et al.; Ciprofloxacin concentrations in serum and in bronchial secretions were studied after single and multiple intravenous administrations for two days in ten patients . The dose given was either 0.75 or 1.5 mg/kg . With the lower dose, the peak concentrations in the bronchial secretions were (mean +/- S.D.) 0.40 +/- 0.29 mg/l after the first injection and 0.35 +/- 0.25 mg/l after the fourth injection . With the higher dose, the corresponding mean peak bronchial concentrations were 0.84 +/- 0.58 and 1.16 +/- 0.86 mg/l respectively . The half-lives of the drug in bronchial secretions ranged from 2.13 to 3.72 h . The penetration of ciprofloxacin into bronchial secretions was excellent as demonstrated by the high ratios of the areas under the concentration curves obtained in the serum and in bronchial secretions which ranged from 0.79 to 1.11.

J Antimicrob Chemother, 1988 Oct, 22 Suppl D, 55 - 63
Comparative in-vitro activity of fleroxacin and other 6-fluoroquinolones against mycobacteria; Salfinger M et al.; The susceptibility of 11 clinical isolates of Mycobacterium tuberculosis, 3 M . kansasii, 3 M . xenopi, 2 M . scrofulaceum, 2 M . marinum, 2 M . malmoense to fleroxacin, ciprofloxacin, norfloxacin, rifampicin, isoniazid, ethambutol, and streptomycin was determined by the standard proportion method (Middlebrook 7H10 agar) . All M . tuberculosis, M . kansasii, M . xenopi, M . scrofulaceum, M . marinum, and M, malmoense isolates including those resistant to conventional antimycobacterials were inhibited by 0.5 mg/l of fleroxacin and ciprofloxacin, the lowest tested concentration . Fleroxacin and ciprofloxacin along with ofloxacin, pefloxacin, ansamycin, clofazimine and cycloserine were also tested against 14 isolates of the M . avium complex . Nine of 14 strains (64%) of the M . avium complex were found susceptible to 4 mg/l of fleroxacin and a similar percentage to the other quinolones . On the basis of its in-vitro potency and its favourable pharmacokinetic properties fleroxacin appears to be sufficiently active to warrant further experimental trials against difficult to treat mycobacteria.

Eur J Clin Microbiol Infect Dis, 1988 Oct, 7(5), 658 - 61
Clinical efficacy of ciprofloxacin versus doxycycline in the treatment of non-gonococcal urethritis in males; van der Willigen AH et al.; In a randomised study the clinical efficacy of ciprofloxacin was compared with that of doxycycline administered in two different dosage schemes to male patients suffering from non-gonococcal urethritis . Fourteen days after completion of therapy (day 21) pyuria was absent in 30 of 100 patients in the ciprofloxacin group; Chlamydia trachomatis was isolated from five and Ureaplasma urealyticum from eight patients . In the 100 mg doxycycline group (n = 60) pyuria was absent in 36 patients (60%) and Ureaplasma urealyticum was isolated from six patients on day 21 . In the 200 mg doxycycline group (n = 45) pyuria was absent in 18 patients (40%) and Ureaplasma urealyticum was isolated from two patients on day 21 . Side-effects were mild and transient in all groups . It is concluded that ciprofloxacin given in a dosage of 1 g for seven days is not effective in the treatment of non-gonococcal urethritis.

Chemioterapia, 1988 Oct, 7(5), 295 - 7
Inhibition of plasmid conjugation by some recently synthetized 4-quinolone compounds; Scazzocchio F et al.; Four fluoroquinolones (norfloxacin, ciprofloxacin, ofloxacin, and pefloxacin) were compared with nalidixic acid for their inhibitory effect on conjugal plasmid transfer . The inhibition was observed in mating experiments using various combinations of drugs at subinhibitory concentrations and 3 different plasmids in the E . coli k12 genetic background . Fluoroquinolones inhibited plasmid transfer to a greater extent than nalidixic acid . Ofloxacin and pefloxacin were consistently the most active agents, causing 90 to 100% inhibition of plasmid transfer in all mating systems studied.

Acta Anaesthesiol Scand, 1988 Oct, 32(7), 590 - 2
Intravenous infusion of midazolam, propofol and vecuronium in a patient with severe tetanus; Orko R et al.; An adult patient with severe tetanus was successfully treated with alternating long-term infusions of propofol (20-80 mg/h, 8 + 3 days) and midazolam (5-15 mg/h, 29 days) for sedation, and with vecuronium infusion (6-8 mg/h, 35 days) for muscle relaxation . In addition, continuous infusion of labetalol (10-20 mg/h, 39 days) was given to control arterial blood pressure . Blood samples were taken daily for assays of propofol, midazolam and vecuronium plasma concentrations . No accumulation of propofol and vecuronium could be detected . There was an increase in liver enzyme activity at the end of the first 8-day propofol infusion . During the 4-week midazolam infusion, there were two marked plasma concentration peaks at times when the infusion rate was fairly stable . These changes coincided with pulmonary infection (C-reactive protein elevated) and ciprofloxacin treatment . The patient awoke rapidly after the last propofol infusion . He was unable to recall anything about his stay in the intensive care unit.

Tubercle, 1988 Sep, 69(3), 193 - 5
In vitro activity of ciprofloxacin in combination with standard antituberculous drugs against mycobacterium tuberculosis; Uttley AH et al.; Chequer-board titrations show that the in vitro activity of ciprofloxacin against Mycobacterium tuberculosis is independent of that of streptomycin, isoniazid, ethambutol and pyrazinamide and confirm that there is antagonism between ciprofloxacin and rifampicin.

Arzneimittelforschung, 1988 Sep, 38(9), 1265 - 7
Penetrability of ofloxacin into cultured epithelial cells and macrophages; Une T et al.; It is well known that the penetration of drugs into host cells is the minimal requirement to exhibit their efficacy against infections with intracellular bacteria . Thus the penetrability of new quinolones including ofloxacin, norfloxacin and ciprofloxacin was evaluated by comparing their intracellular and extracellular activities by the use of cell infection systems in vitro . It was evidenced that the new quinolones tested were penetrable into both epithelial cells and macrophages, however, ofloxacin was more penetrable than norfloxacin and ciprofloxacin into both types of cells which serve the nest for proliferation of intracellular bacteria.

J Antimicrob Chemother, 1988 Sep, 22 Suppl C, 97 - 107
Overview of drug interactions with the quinolones; Davey PG; Drug interactions with the quinolones are of two types: pharmacokinetic and pharmacodynamic . Pharmacokinetic interactions include inhibition of absorption of quinolones by aluminium and magnesium containing antacids and inhibition of metabolism of other drugs by quinolones . Norfloxacin and ofloxacin are not extensively metabolized and do not inhibit drug metabolism; ciprofloxacin and enoxacin reduce theophylline clearance in normal subjects by less than 50% and greater than 50% respectively . Ciprofloxacin inhibits the metabolism of caffeine, theophylline and antipyrine . The latter is a marker of broad substrate specificity and, until proved otherwise, it would be prudent to avoid combination of ciprofloxacin with drugs which are metabolized and have a low therapeutic index . In addition to theophylline, these include cyclosporin, phenytoin and warfarin . There is evidence that the elderly and patients with liver disease are particularly susceptible to kinetic interactions with ciprofloxacin . In contrast, there is no evidence to suggest that ofloxacin is likely to impair hepatic drug elimination . Enoxacin does not impair the metabolism of chlorpropamide or glibenclamide, it is therefore unlikely that any of the quinolones will interact with sulphonylurea hypoglycaemic drugs . A pharmacodynamic interaction has been demonstrated in vitro between quinolones and non-steroidal anti-inflammatory drugs (NSAIDS) or theophylline . All of these drugs inhibit binding of radio-labelled gamma-amino-butyric acid to mouse synaptic membranes and combinations of quinolones with NSAIDS or theophylline are synergistic . Convulsions have been reported in patients who received a combination of enoxacin with either fenbufen, a NSAID, or theophylline . Like theophylline, NSAIDS undergo hepatic metabolism, so the clinical interaction may be the result of combined pharmacokinetic and pharmacodynamic interactions . Drug-interactions with quinolones are a clinically important problem . Drugs, such as ofloxacin, which do not impair hepatic metabolism of other drugs, have a clinically significant advantage over other quinolones . The pharmacodynamic interaction between quinolones and other GABA inhibitors is extremely poorly documented; further in-vitro, animal and clinical studies are urgently required.

J Antimicrob Chemother, 1988 Sep, 22 Suppl C, 109 - 14
Interaction between the fluoroquinolones and the bronchodilator theophylline; Wijnands WJ et al.; This review summarizes the available data on the influence of ofloxacin on the metabolic clearance of the bronchodilator theophylline . At the moment, several new fluoroquinolone derivatives, such as ofloxacin, ciprofloxacin, pefloxacin, and enoxacin are being clinically tested in respiratory tract infections . Enoxacin causes a strong and clinically important decrease (60%) of the total body clearance of theophylline . Ciprofloxacin and pefloxacin show the same effect, though to a smaller degree (30%) . During treatment with these three agents clinical signs and symptoms of theophylline toxicity have been reported . However, no signs of increased plasma theophylline concentrations have been observed during concomitant treatment with ofloxacin and theophylline . Further research into the mechanism of this interaction has demonstrated that quinolones compete with cytochrome P450 related isoenzymes, resulting in a decreased demethylation of theophylline . Whereas a slight influence on these enzymes could be demonstrated for ofloxacin when the drug was administered in very high concentrations to rats, no significant influence on theophylline metabolic pathways in man has been measured, when ofloxacin was administered in doses up to 800 mg daily.

Br J Clin Pharmacol, 1988 Aug, 26(2), 191 - 4
Predicting the ciprofloxacin-theophylline interaction from single plasma theophylline measurements; Bachmann KA et al.; The effect of ciprofloxacin treatment on theophylline clearance was evaluated with a theophylline multiple dose, multiple sample protocol and with a single dose, single sample protocol . The object was to determine whether a single dose, single sample protocol for estimating theophylline clearance could be used as a screening strategy for evaluating host factor influences on theophylline clearance . Ciprofloxacin (750 mg per os) was administered every 12 h for nine doses in the multidose study and every 12 h for seven doses in the single dose protocol . Subjects were sixteen healthy, non-smoking young adult males . The oral clearance of theophylline at steady state, (CL/F)ss, decreased from a mean (+/- s.d.) value of 0.035 (+/- 0.008) 1 h-1 kg-1 to 0.024 (+/- 0.004) 1 h-1 kg-1 during ciprofloxacin treatment . Single sample estimates of theophylline clearance, CL/F, similarly decreased from 0.040 (+/- 0.014) 1 h-1 kg-1 to 0.018 (+/- 0.008) 1 h-1 kg-1 . Mean theophylline clearances were significantly different when comparing control with ciprofloxacin treatment means (P less than 0.01), but were not different when comparing single sample vs multiple sample clearances for a given treatment (i.e . control or ciprofloxacin) . It is concluded that a single dose, single sample strategy may be used in screening for host-factor influences on theophylline clearance.

Antimicrob Agents Chemother, 1988 Jul, 32(7), 982 - 5
Hepatobiliary kinetics and excretion of ciprofloxacin; Parry MF et al.; The biliary excretion and metabolism of ciprofloxacin was studied in 25 hospitalized patients: 19 undergoing routine cholecystectomy and 6 with indwelling biliary drainage catheters . An intravenous dose of 200 mg of ciprofloxacin given 2.5 to 3.0 h prior to cholecystectomy resulted in concentrations in common duct bile, gallbladder bile, and gallbladder wall of 5.69 +/- 4.8, 5.43 +/- 3.34, and 2.52 +/- 1.30 micrograms/g, respectively, all at least fourfold greater than simultaneous concentrations in serum . Ciprofloxacin concentrations in common duct bile exceeded peak concentrations in serum in all but two patients with common duct obstruction . Multiple preoperative doses of ciprofloxacin prior to cholecystectomy increased concentrations in gallbladder bile by eightfold . Six patients with indwelling biliary drainage catheters also received 200 mg of ciprofloxacin intravenously . Less than 1% of the administered dose was excreted in bile as unchanged ciprofloxacin, and there was extensive metabolism . However, peak ciprofloxacin concentrations of 2.83 +/- 0.76 micrograms/ml in serum produced peak concentrations of 10.69 +/- 5.30 micrograms/ml in bile within 1.5 h after infusion and maintained concentrations of at least 0.5 microgram/ml in common duct bile for over 12 h in all patients . It appears that ciprofloxacin concentrations in bile will exceed the MICs for most susceptible biliary pathogens for a period of at least 12 h after a 200-mg intravenous dose.

J Antimicrob Chemother, 1988 Jul, 22(1), 61 - 7
The effect of ciprofloxacin on antipyrine metabolism; Ludwig E et al.; The effect of multiple-dose ciprofloxacin on antipyrine metabolism was studied in patients suffering from bacterial infections . The patients were given antipyrine 15 mg/kg intravenously before and after ciprofloxacin treatment . The dosage of ciprofloxacin was 500 mg bd by mouth for 8-10 days . Blood samples were taken at 0, 2, 4, 6, 10 h . Antipyrine total clearance was significantly decreased after ciprofloxacin treatment (0.85 +/- 0.45 vs . 0.52 +/- 0.24 ml/min/kg): elimination rate constants for antipyrine were decreased in all patients after ciprofloxacin, whereas no change in volume of distribution was observed . The average half-life of antipyrine was increased from 9.45 +/- 3.74 h to 14.92 +/- 3.32 h . In two males with advanced chronic hepatic failure the antipyrine half-lives were extremely prolonged . Our results support the hypothesis that ciprofloxacin inhibits intrinsic hepatic drug-metabolizing capacity and may be a source of clinically important drug interactions, particularly in patients with liver disease.

Antimicrob Agents Chemother, 1988 Jun, 32(6), 936 - 7
No cytogenetic effects of quinolone treatment in humans; Mitelman F et al.; Cytogenetic effects of ciprofloxacin (500 to 2,000 mg daily) and ofloxacin (200 mg daily) were studied in lymphocytes from 31 patients treated for 1 to 10 weeks . Blood samples for cytogenetic analysis were taken before the start of treatment from all patients, after 1 week from 25 patients, and after 2, 4, 6, and 10 weeks from six patients . No chromosome-damaging effect could be demonstrated in any treatment group . The mean aberration yields for each cytogenetic parameter studied and the total number of aberrations were all normal at each sampling occasion.

Arzneimittelforschung, 1988 May, 38(5), 727 - 9
{The effect of ciprofloxacin on epinephrine and collagen induced thrombocyte aggregation in vitro on dialysis patients}; Reuter HD et al.; In recent investigations it was found that ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7 (1-piperazinyl)-3-fiquinoline-carboxylic acid, Ciprobay) in concentrations similar to maximal levels obtained in the serum of patients with normal renal function after application of therapeutic doses and 4- to 5fold such concentrations does not influence aggregation induced by epinephrine and collagen in platelet rich plasma of healthy subjects . Because in literature there are several reports about disturbances of platelet aggregation in patients with renal failure treated with antibiotics and because renal failure often is accompanied by defect platelet function the effect of ciprofloxacin on epinephrine and collagen induced aggregation was studied in platelet rich plasma of patients with chronic renal failure undergoing dialysis . Compared to platelets from patients with renal failure which had been incubated with saline instead of ciprofloxacin, patients platelets under the influence of ciprofloxacin did not show any significant differences . From this we conclude that the defect which may be present in platelets of patients with chronic renal failure is not further increased by ciprofloxacin.

Pathol Biol (Paris), 1988 May, 36(5), 496 - 9
{In vitro activity of new quinolones against Mycoplasma pathogenic to humans}; Renaudin H et al.; The in vitro activity of new quinolones was evaluated against Mycoplasma pneumoniae (10 strains) and Mycoplasma hominis (approximately equal to 70 strains) by agar dilution, and against Ureaplasma urealyticum (approximately equal to 115 strains) by broth dilution . The static effect of pefloxacin, ofloxacin, ciprofloxacin, enoxacin was investigated for all the strains . Rosoxacin was included in the tests for U . urealyticum and M . hominis . Pefloxacin, ofloxacin, ciprofloxacin and enoxacin were within the same range of sensitivity for M . pneumoniae; the minimal inhibitory concentrations (MICs) of the 10 strains were 1 mg/l for ciprofloxacin, 2 mg/l for pefloxacin, MICs range was (0.05-1 mg/l) for ofloxacin and (0.5-4 mg/l) for enoxacin . Ciprofloxacin was the most active compound against M . hominis; MICs range and mode MICs were respectively in mg/l: (0.1-1) 0.5 for ciprofloxacin, (0.2-2) 0.5 for ofloxacin, (0.5-2) 1 for pefloxacin, (0.5-8) 2 for enoxacin, (2-16) 2 for rosoxacin . Ofloxacin was the most active compound against U . urealyticum; MICs range and mode MICs were respectively in mg/l: (0.2-2) 1 for ofloxacin, (0.1-8) 2 for rosoxacin, (0.5-8) 4 for pefloxacin, (1-16) 4 for ciprofloxacin, (2-32) 8 for enoxacin . No difference could be observed between tetracycline sensitive or resistant strains.

Infection, 1988, 16(1), 54 - 7
Ciprofloxacin concentration in the rabbit aqueous humor and vitreous following intravenous and subconjunctival administration; Behrens-Baumann W et al.; 12 mg (6 ml) ciprofloxacin were intravenously administered to rabbits . Using high-pressure-liquid-chromatography the concentration in serum, aqueous humor and vitreous were measured after 1, 4, 10 and 24 h . The mean serum levels were 0.698 mg/l and 0.0425 mg/l after 1 and 10 h, respectively . The drug reached mean levels in the aqueous humor of 0.0595 mg/l and 0.0073 mg/l, respectively . Concerning the subconjunctival application 1 mg (0.5 ml) ciprofloxacin was injected either epibulbar near the limbus corneae or under the conjunctiva of the lower fornix . The mean aqueous humor levels were 0.887 mg/l and 0.094 mg/l after 1 and 10 h, respectively, following epibulbar injection . In contrast, the "fornix-injection" produced mean levels of 0.0267 mg/l and 0.025 mg/l in the aqueous humor after 1 and 10 h, respectively . The concentration of ciprofloxacin in the vitreous was near the detection limit following every method of administration of the drug . The importance of differentiating between epibulbar subconjunctival application and the injection under the conjunctiva of the fornix is discussed.

Antimicrob Agents Chemother, 1988 Jan, 32(1), 75 - 7
Impact of ciprofloxacin on theophylline clearance and steady-state concentrations in serum; Schwartz J et al.; The effect of a multiple-dose regimen of oral ciprofloxacin (750 mg every 12 h for 11 doses) on the clearance and steady-state concentrations of theophylline in trough (predose) serum was evaluated in nine healthy male subjects, each serving as his own control . Theophylline was taken as a sustained release tablet per os in a dose of 200 mg every 12 h for 19 doses . Theophylline concentrations in serum were measured immediately before each theophylline dose . Ciprofloxacin was administered on study day 4 through the first dose of study day 8 . Theophylline concentrations in serum were also measured on study days 3, 6, 8, and 10 at the following times after the first dose of each day: 0, 0.25, 0.50, 1, 2, 4, 6, 8, 10, and 12 h . Steady-state theophylline concentrations in trough serum were significantly higher during ciprofloxacin treatment (day 8) than before (day 3) or after (day 10) ciprofloxacin administration (P less than 0.01) . Likewise, theophylline clearance was significantly slower (P less than 0.01) during ciprofloxacin treatment (day 8) than before it (day 3) or after it (day 10) . The magnitude of ciprofloxacin-induced changes was approximately 30% . These results suggest that a multidose regimen of ciprofloxacin significantly slows the clearance of theophylline and elevates theophylline concentrations in serum.

Drugs Exp Clin Res, 1988, 14(1), 9 - 18
In-vitro activity of antifungal agents in combination with four quinolones; Petrou MA et al.; The antifungal activity of amphotericin B (AMB), mepartricin (MEPA), 5-fluorocytosine (5FC) and three imidazoles was tested in combination with each of four quinolones against 60 clinical yeast isolates . The inhibitory activity of AMB and MEPA was marginally enhanced by the azaquinolones, nalidixic acid (NAL) and enoxacin (ENO), but there was antagonism when combined with the fluorinated quinolones ciprofloxacin (CIP) and norfloxacin (NOR) . All quinolones except NAL partially antagonised 5FC . Miconazole (MCZ), ketoconazole (KTZ) and itraconazole (ITZ) were each found to be synergistic with low concentrations of the quinolones, and also with high concentrations of NAL and ENO, but were strongly antagonised by high concentrations of CIP and NOR.

Infection, 1988, 16 Suppl 1, S55 - 6
Bacterial infections of the skin treated with ciprofloxacin; Gorkiewicz-Petkow A et al.; Bacterial infections of the skin or soft tissue responded to ciprofloxacin 500 mg tablets b.i.d . The treatment was well tolerated and effective, so that this drug can be recommended in cutaneous infections caused by sensitive bacteria.

Rev Infect Dis, 1988 Jan-Feb, 10 Suppl 1, S241 - 7
Pharmacokinetics and efficacy of the new quinolones in infections of the eye, ear, nose, and throat; Barza M; A review of published data indicates that the new quinolones readily penetrate the tissues and secretions of the upper respiratory tract . The concentrations of ciprofloxacin and ofloxacin in tonsillar tissue and the concentrations of ofloxacin in the mucosa of the paranasal sinuses generally exceeded the peak concentrations of these agents in serum after oral administration of the drugs . Good penetration was noted for ciprofloxacin into nasal secretions, ofloxacin into tears, and various quinolones into saliva . Penetration into ocular humors appears to be moderate . Reports in English concerning clinical trials of the new fluoroquinolones in the treatment of infections of the eyes, ears, nose, and throat are sparse, but a number of studies of ofloxacin have been published in Japanese . The data suggest that the new quinolones may be useful for the treatment of acute sinusitis and chronic suppurative otitis media . However, studies comparing these agents with more established drugs and using carefully defined criteria for diagnosis and for evaluation of the response to treatment are needed.

Drugs Exp Clin Res, 1988, 14(5), 333 - 4
In vitro influence of charcoal on ciprofloxacin activity; Torre D et al.; The effect of charcoal-containing media on ciprofloxacin (BAY o 9867) has been evaluated . The minimal inhibitory concentrations of ciprofloxacin are increased by the presence of charcoal, thus a correction factor has to be calculated to know the real efficacy of the drug, especially in life-threatening infections such as pneumonia due to Legionella spp.

Eur J Clin Pharmacol, 1988, 35(6), 651 - 6
4-quinolones inhibit biotransformation of caffeine; Harder S et al.; The pharmacokinetics of caffeine, including formation of its major metabolite paraxanthine in plasma, has been investigated in 12 healthy males (age 20-40 years) alone and during co-administration of the 4-quinolones ofloxacin, norfloxacin, pipemidic acid, ciprofloxacin, and enoxacin; ciprofloxacin and enoxacin were given in 3 different dose levels . The naphthyridine derivative enoxacin and the pyrido-pyrimidine derivative pipemidic acid had caused marked inhibition of caffeine and paraxanthine metabolism, whereas the genuine quinolone derivatives norfloxacin and ciprofloxacin had little effect, and the pyrido-benzoxacine derivative ofloxacin had no detectable effect . The different molecular and spatial structures of the compounds appear to be responsible for the differences in inhibitory potency.

Pharm Weekbl Sci, 1987 Dec 11, 9 Suppl, S72 - 5
The influence of the 4-quinolones ciprofloxacin, pefloxacin and ofloxacin on the elimination of theophylline; Wijnands WJ et al.; Pharmacokinetic parameters of the bronchodilator theophylline were assessed in eight patients with chronic obstructive lung disease when administered alone and when comedicated with ciprofloxacin 500 mg twice daily, ofloxacin 400 mg twice daily, or pefloxacin 400 mg twice daily . Compared to the control period, in which only theophylline was administered, the total body clearance of theophylline decreased significantly during ciprofloxacin (30.4%) and pefloxacin (29.4%) coadministration, whereas no change of the renal clearance of theophylline occurred . Ofloxacin did not influence the pharmacokinetic parameters of theophylline . From these observations it is concluded that ciprofloxacin and pefloxacin reduce the metabolic clearance of theophylline.

Pharm Weekbl Sci, 1987 Dec 11, 9 Suppl, S23 - 5
Influence of haemodialysis on the pharmacokinetics of ciprofloxacin; Samsom JP; The elimination of ciprofloxacin from serum was studied in 16 patients (10 F, 6M, age 44-70 years) with end stage renal disease, treated with haemodialysis . The dosage of ciprofloxacin was 200 mg i.v . given by bolus injection (10 patients) or 250 mg orally (6 patients) on a day without and a day with dialysis (8 hours before dialysis was started) . Samples were taken at regular intervals from the arteriovenous shunt and from venous peripheral blood . Concentrations of ciprofloxacin were measured by a biological assay . The mean peak serum levels after 200 mg i.v . were 3.5 mg/l measured 0.5 hour after the gift . After an oral dose of 250 mg the mean peak serum level measured one hour after the gift amounted to 1.5 mg/l . The serum half life was 8.5 h without dialysis and 5.5 h with dialysis . It was calculated from AUC values during dialysis that about 15% of the drug was eliminated by the artificial kidney.

Pharm Weekbl Sci, 1987 Dec 11, 9 Suppl, S87 - 9
The use of fluoroquinolones in chronic otitis suppurativa; van de Heyning PH et al.; The present review covers fluoroquinolone usage in chronic otitis suppurativa (COS) in case of chronic otitis media, cholesteatoma, radical mastoid cavity infection and chronic or relapsing otitis externa . A total of six publications were included in the final evaluation . Enoxacin was effective in 35%; ciprofloxacin (five publications) was used in 82 patients with 67% effectivity in otitis externa and otitis media and 61% effectivity in radical mastoid cavity infection . No serious adverse reactions were reported . The promising efficacy of otitis media and otitis externa and safety profile needs further confirmation in double blind prospective clinical studies, that will provide a firm basis for changing the current treatment schedules of COS.

Pharm Weekbl Sci, 1987 Dec 11, 9 Suppl, S82 - 6
Quinolones in the treatment of gonorrhoea and Chlamydia trachomatis infections; Stolz E et al.; The results of two therapeutic trials in female patients with uncomplicated urogenital gonorrhoea (A) and in male patients with uncomplicated urethral gonorrhoea (B) treated with either 200 mg and 400 mg enoxacin orally, of one therapeutic trial in male patients with uncomplicated urogenital gonorrhoea treated with either 250 mg or 500 mg ciprofloxacin orally (C) and of one therapeutic trial in male patients with non-gonococcal urethritis (NGU) treated with ciprofloxacin 1 g daily during seven days (D) are presented and compared with the results of other investigators . The cure rate in study A was 100% (n = 40) in the 400 mg group and 95.7% (n = 46) in the 200 mg group . The cure rate in study B was 92% (n = 78) in the 400 mg group and 90% (n = 77) in the 200 mg group . In both studies no antichlamydial effect of enoxacin was observed . The cure rates in study C were 100% with 250 and 500 mg . An antichlamydial effect seemed to be present . In studies A, B and C side effects were minor and rare and were mainly nausea and headache . In study D (100 patients suffering from NGU) disappearance of Chlamydia trachomatis and Ureaplasma urealyticum one day after the end of treatment was observed in 29 of 32 (91%) and 28 of 32 (88%) cases, respectively . Pyuria disappeared in 44% and 74% of the patients showed clinical cure . However, two weeks after the end of treatment Chlamydia trachomatis and Ureaplasma urealyticum were observed in respectively six and eight cases . In 30% pyuria was still absent . Side effects were only minor.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharm Weekbl Sci, 1987 Dec 11, 9 Suppl, S16 - 22
Pharmacokinetics of the newer fluoroquinolones; Brouwers JR; A large number of pharmacokinetic studies have been carried out using 4-quinolones in order to estimate total and renal clearance, to examine tissue penetration, to establish suitable dosage regimens and to determine the influence of kidney and liver impairment on the pharmacokinetic behaviour . Although the quinolones are poorly water soluble over the physiological pH range (6-8) they are well absorbed following oral administration . Ofloxacin is almost completely absorbed and ciprofloxacin has been shown to have an absolute bioavailability of 0.70 . Plasma protein binding varies greatly from quinolone to quinolone ranging from about 10% in the case of norfloxacin to more than 90% in the case of nalidixic acid . Penetration of the quinolones into the prostate is generally good . Most quinolones, too, have been shown to penetrate blister fluid rapidly and this model has proved useful in distribution studies . Some quinolones, like ofloxacin, are excreted largely unchanged while others like pefloxacin and acrosoxacin, are almost completely metabolized . Conjugation to very water-soluble glucuronides is not common although other types of metabolites have been shown . Little information appears to have been published on the effect of liver disease on the metabolism of the quinolones . This must be an important consideration for this type of drugs which are subject to hepatic transformation . The pharmacokinetic behaviour of quinolones in patients with impaired renal function has been extensively studied . The interaction of food on the absorption does not seem to be great, there is however evidence of a drug interaction between theophylline and some of the newer quinolones . Sucralfate and antacids containing Mg2+ or (and) Al3+-ions can markedly impair the absorption of quinolone antibiotics.

J Antimicrob Chemother, 1987 Dec, 20(6), 875 - 81
Comparison of ciprofloxacin and rifampicin in experimental Legionella pneumophila pneumonia; Havlichek D et al.; We evaluated intraperitoneal ciprofloxacin and rifampicin alone and as combination therapy in experimentally induced Legionella pneumophila pneumonia in guinea pigs . Intraperitoneal treatment began 48 h after intratracheal inoculation of 3 X 10(6) L . pneumophila and consisted of sterile saline (0.3 ml bid), ciprofloxacin (30 mg/kg bid), rifampicin (10 mg/kg/bid), or ciprofloxacin plus rifampicin (same doses) . Animals were treated for five days and survivors killed after 11 days . Quantitative lung cultures were done post mortem . Respective mean and median days of animal survival were increased by treatment with ciprofloxacin plus rifampicin (8.4 and 9.5 days), ciprofloxacin (8.2 and 7.5 days), or rifampicin (8.3 and 7.5 days), compared with controls (5.5 and 5.0 days) . Compared with control animals (log rank test) survival was improved by treatment with ciprofloxacin plus rifampicin (P less than or equal to 0.047) ciprofloxacin (P less than or equal to 0.047) or rifampicin (P less than or equal to 0.047) . Quantitative lung cultures (cfu/g) were also decreased by treatment with ciprofloxacin plus rifampicin (2.0 X 10(4)), ciprofloxacin (5.4 X 10(4)), or rifampicin (1.7 X 10(4)) compared with controls (3.2 X 10(8)) . No differences in survival, quantitative lung cultures, or animal weights were noted between treatment groups . This study demonstrates that ciprofloxacin is as effective as rifampicin in the treatment of experimentally induced L . pneumophila pneumonia and that the combination of ciprofloxacin plus rifampicin has no advantages over single agent therapy in this model.

Chemioterapia, 1987 Dec, 6(6), 437 - 9
In vitro susceptibility of Mycobacterium tuberculosis to ofloxacin and ciprofloxacin in combination with rifampin and isoniazid; Casal M et al.; The in vitro susceptibility of Mycobacterium tuberculosis to new quinolones, ofloxacin and ciprofloxacin, alone and in combination with rifampin or isoniazid, was studied by the agar dilution method . At a concentration of 1 mg/l or lower of ofloxacin and ciprofloxacin, 90% of the strains were inhibited . A synergistic effect with rifampin and with isoniazid was demonstrated.

J Antimicrob Chemother, 1987 Nov, 20(5), 729 - 34
Decrease of caffeine elimination in man during co-administration of 4-quinolones; Stille W et al.; The single dose pharmacokinetics of caffeine (220-230 mg per dose) were investigated in 12 healthy male volunteers before and during treatment with ofloxacin (200 mg bd), ciprofloxacin (250 mg bd) and enoxacin (400 mg bd) with a cross-over study design . None of the parameters: mean elimination half-life (T1/2el), Cmax, total body clearance (Cltot) and the volume of distribution (aVd) of caffeine were noticeably altered by administration of ofloxacin . Striking changes were observed, however, after administration of enoxacin: the T1/2el was prolonged by as much as 260%, the Cmax increased by 41%; the aVd was reduced by 20% and Cltot by 78% (mean values) . Treatment with ciprofloxacin led to a prolongation of T1/2el by 15%, to a decrease of aVd by 25% and to a 33% decrease of Cltot . The results of this intra-individual comparison of caffeine pharmacokinetic data demonstrate that treatment with ciprofloxacin and enoxacin may have a significant inhibitory effect on caffeine elimination.

Antimicrob Agents Chemother, 1987 Nov, 31(11), 1787 - 90
Effects of antacids and dialysate dwell times on multiple-dose pharmacokinetics of oral ciprofloxacin in patients on continuous ambulatory peritoneal dialysis; Golper TA et al.; Six stable patients on continuous ambulatory peritoneal dialysis were evaluated for the appearance of ciprofloxacin in their peritoneal dialysate following oral ingestion of 750 mg of the drug every 12 h for four doses . Three subjects participated in this study twice, once while taking and once while abstaining from phosphate-binding aluminum antacids . Subjects tolerated the medication without evidence of toxicity . Food may have delayed or decreased the absorption of ciprofloxacin, whereas antacids definitely decreased the absorption of the drug . Peak concentrations in serum noted in the absence of antacids ranged from 2.9 to 6.4 micrograms/ml, and peak concentrations in dialysate in the absence of antacids ranged from 1.8 to 4.5 micrograms/ml . Peak ciprofloxacin concentrations in serum achieved in subjects taking antacids were 14 to 50% of those achieved in subjects without antacids . The peak concentrations in dialysate achieved in subjects on antacids were 8 to 33% of those observed in subjects off antacids . The clearance of ciprofloxacin by continuous ambulatory peritoneal dialysis represented 2% of the total body (systemic) clearance . Simultaneous ratios of concentration in dialysate to concentration in serum (D/S) were determined at various durations of dialysate dwelling within the peritoneum . A progressive rise of the D/S ratio was noted as dwell time increased . At 4 h D/S was 0.57 +/- 0.07 (mean +/- standard error of the mean; n = 9), and at 8 h it was 0.75 +/- 0.04 (n = 26) . Long-dwell exchanges may be necessary to achieve reasonable concentrations of orally ingested ciprofloxacin in dialysate.

J Antimicrob Chemother, 1987 Nov, 20(5), 631 - 8
Induction of the SOS response by new 4-quinolones; Phillips I et al.; The 4-quinolones ciprofloxacin, difloxacin, enoxacin, norfloxacin, ofloxacin, and nalidixic acid were found to induce the SOS response in qualitative and quantitative tests on Escherichia coli K12 containing the sfiA::lacZ gene fusion . Maximum induction of the SOS-response was observed with the quinolone concentrations that produced the most killing . There was also a modest increase in the rate of mutation in the lactose and galactose operons in a GalE- background, provided there was a functioning SOS system.

Antimicrob Agents Chemother, 1987 Oct, 31(10), 1651 - 5
In vitro activity of ciprofloxacin against aerobic bacteria isolated in a southern European hospital; Cornaglia G et al.; The activity of ciprofloxacin was evaluated against 1,204 isolates freshly isolated in Southern Europe, including 193 isolates of 10 species never studied before . Ciprofloxacin proved more active than other quinolones and very active in absolute terms against the 10 new species and showed against the other species an activity close to that reported for isolates from other geographic areas.

Arzneimittelforschung, 1987 Jul, 37(7), 797 - 8
Penetration of ciprofloxacin into parotid gland tissue and parotid saliva; Maier H et al.; The penetration of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid (ciprofloxacin, Bay o 9867, Ciprobay) into parotid gland tissue and parotid saliva of the rat after intravenous administration (6 mg/kg body weight) was studied . 2 h after bolus injection ciprofloxacin mean levels in parotid gland tissue (0.60 mg/l) nearly reached 2-fold mean blood levels (0.36 mg/l) . In parotid saliva the mean concentration of the gyrase inhibitor (0.20 mg/l) was lower than in blood, however, still high enough to be effective against the pathogens which most often cause inflammation of the parotid gland.

Antimicrob Agents Chemother, 1987 Jun, 31(6), 956 - 8
Effect of dose size on bioavailability of ciprofloxacin; Plaisance KI et al.; We evaluated the bioavailability of ciprofloxacin at two dose sizes in eight healthy volunteers . Each volunteer was given 200 mg of ciprofloxacin both orally and intravenously in a randomized crossover fashion and 750 mg orally . Bioavailability at the two doses was similar: 69 and 69.1% for the 200- and 750-mg doses, respectively . However, the bioavailability observed with the 750-mg dose was significantly more variable than that observed with the 200-mg dose . Between 375 and 700 mg of ciprofloxacin reached the systemic circulation after administration of the 750-mg dose, with no evidence of adverse reactions.

J Antimicrob Chemother, 1987 Jun, 19(6), 781 - 90
Comparative effects of quinolones on human mononuclear leucocyte functions; Roche Y et al.; The effects of three quinoline derivatives--pefloxacin, ciprofloxacin and ofloxacin--were investigated in mitogen-stimulated human peripheral blood mononuclear leucocytes (MNL) . At concentrations of 50 mg/l or more, pefloxacin, ciprofloxacin or ofloxacin significantly inhibited MNL proliferation in response to phytohaemagglutinin . This inhibition was more marked with ciprofloxacin than pefloxacin or ofloxacin . To determine the possible mechanism(s) involved in the inhibition of MNL proliferation following exposure to pefloxacin, ciprofloxacin or ofloxacin, we assessed (1) interleukin-1 (IL-1) activity in supernatants from monocytes treated with the quinolones and (2) the effects of 2-mercaptoethanol (2-ME) a thiol compound which acts as an antioxidant agent and the effect of indomethacin (INDO) an inhibitor of prostaglandin E2 synthesis . 2-ME and INDO did not prevent the decrease in the proliferation . IL-1 activity was shown to be decreased for the same range of antibiotic concentrations as observed for the inhibition of MNL proliferation . Cellular viability of the MNL or monocytes was not modified by any of the quinolones at the concentrations tested . Taken together, these results suggest that pefloxacin, ciprofloxacin and ofloxacin act as immunomodulators . The mechanism involved with the cascade of events that leads to the lymphocyte proliferation and the clinical relevance need further investigation.

Biochemistry, 1987 May 19, 26(10), 2870 - 8
Processivity of the DNA polymerase alpha-primase complex from calf thymus; Hohn KT et al.; The processivity of the DNA polymerase alpha-primase complex from calf thymus was analyzed under various conditions . When multi-RNA-primed M13 DNA was used as the substrate, the DNA polymerase alpha-primase complex was found to incorporate 19 +/- 3 nucleotides per primer binding event . This result was confirmed by product analysis on sequencing gels following DNA synthesis on poly(dT) X (rA)10 . The processivity depends strongly on the assay conditions but does not correlate with enzymic activity . Lowering the concentration of Mg2+ ions to less than 2 mM increases the processivity to 60 . Replacing Mg2+ by 0.2 mM Mn2+ results in 90 nucleotides being incorporated per primer binding event . Neither the presence of ATP nor the addition of noncognate deoxynucleotide triphosphates affects the processivity of the DNA polymerase alpha-primase complex . Lower processivity was induced by lowering the reaction temperature, by adding spermine, spermidine, or putrescine, in the presence of the antibiotics novobiocin and ciprofloxacin, by adding Escherichia coli single-stranded DNA binding protein, or by adding calf thymus topoisomerase II and RNase H . Three single-stranded DNA binding proteins from calf thymus, including unwinding protein 1, do not affect processivity to any significant extent . Freshly prepared DNA polymerase alpha-primase complex exhibits in addition to its processivity of 20 further discrete processivities of about 55, 90, and 105 . This result suggest that further subunits of the polymerase alpha-primase complex are necessary to reconstitute the holoenzyme form of the eukaryotic replicase.

Diagn Microbiol Infect Dis, 1987 May, 7(1), 89 - 91
In vitro activity of ciprofloxacin and ofloxacin against the Mycobacterium avium-intracellulare complex; Johnson SM et al.; The in vitro activity of ciprofloxacin and ofloxacin against strains of Mycobacterium avium-intracellulare complex were studied by the standard 1% proportion method . Thirty-eight of 100 strains (30%) were inhibited by ciprofloxacin at 2 micrograms/ml and 11 of 30 strains (37%) were inhibited by ofloxacin at 8 microm/ml . Patients having these more susceptible isolates may potentially benefit from therapy with these agents {corrected}.

J Antimicrob Chemother, 1987 May, 19(5), 617 - 22
Activity of ciprofloxacin against Mycobacteria in vitro: comparison of BACTEC and macrobroth dilution methods; Trimble KA et al.; Various clinical isolates of mycobacteria were tested for susceptibility to ciprofloxacin by a standard macrobroth dilution test and the radiometric BACTEC method . Agreement between the two test systems was species dependent: Mycobacterium tuberculosis (80%), M . kansasii with M . scrofulaceum (30%), M . avium-intracellulare (20%), and 0% for the rapidly growing mycobacteria . Most mycobacterial strains other than M . tuberculosis were susceptible to the breakpoint ciprofloxacin concentration of 2 mg/l as determined by BACTEC MICs, whereas none were susceptible by macrobroth testing . Seven of nine M . tuberculosis isolates were susceptible by either method . Ciprofloxacin merits further study as a potential antimycobacterial agent.

J Antimicrob Chemother, 1987 May, 19(5), 611 - 5
In-vitro activity of six fluorinated quinolones against Mycobacterium tuberculosis; Berlin OG et al.; Thirty-five clinical isolates of Mycobacterium tuberculosis, 24 susceptible and 11 resistant to conventional primary antituberculous drugs, were tested against six new quinolones . The mode MICs of isoniazid susceptible organisms on 7H11 agar for ciprofloxacin, ofloxacin, enoxacin, norfloxacin, CI-934 and A56620 were 1.0, 1.0, 2.0, 2.0, 1.0 and 1.0 mg/l, respectively . Strains resistant to isoniazid and other antituberculous agents were usually inhibited within one dilution of these values . These new quinolones could serve as alternate therapeutic agents or they may accelerate the antimycobacterial effects of conventional chemotherapy; these hypotheses should now be tested in experimental infections.

Am J Med, 1987 Apr 27, 82(4A), 115 - 8
Ciprofloxacin increases serum levels of theophylline; Raoof S et al.; During a clinical trial of orally administered ciprofloxacin in respiratory tract infections, changes in serum theophylline levels were evaluated in 33 hospitalized patients who also required theophylline therapy . Patients received intravenous theophylline in standard titrated doses and 750 mg of oral ciprofloxacin twice daily . Serum theophylline levels in all patients were measured before and during ciprofloxacin therapy . The mean serum pretreatment theophylline level was 7.8 +/- 4.6 micrograms/ml; during ciprofloxacin therapy, the level increased to 14.6 +/- 7.4 micrograms/ml . Twenty of the 33 (61 percent) patients evaluated had increases in serum theophylline levels by a mean value of 10.5 micrograms/ml . In 30 percent of patients who experienced increases, theophylline concentrations were in the toxic range . This occurred more frequently in elderly patients with chronic obstructive pulmonary disease . In light of the frequency and potential severity of this interaction, careful monitoring of serum theophylline levels in patients receiving theophylline and ciprofloxacin is recommended.

Am J Med, 1987 Apr 27, 82(4A), 103 - 7
Tissue penetration and metabolism of ciprofloxacin; Wise R et al.; The tissue penetration of ciprofloxacin was studied by two methods . Penetration into inflammatory fluid following oral administration (500 mg) was 117 percent; following intravenous administration (100 mg), penetration was 121 percent . The penetration of ciprofloxacin into uninflamed peritoneum following intravenous administration (100 mg) was 95 percent.

Am J Med, 1987 Apr 27, 82(4A), 311 - 6
Treatment of nongonococcal urethritis with ciprofloxacin; Fong IW et al.; A randomized, double-blind study was performed in 225 men with nongonococcal urethritis or postgonococcal urethritis, in which the efficacy of ciprofloxacin (750 mg twice daily for seven days) was compared with that of doxycycline (100 mg twice daily for seven days) . Of the 145 evaluable patients completing three weeks or more of follow-up or reaching an end point, 74 patients received doxycycline and 71 received ciprofloxacin . Chlamydia trachomatis and mixed infections with Ureaplasma urealyticum were more frequent in the cip, ofloxacin group, but the differences were not significant . The overall cure rates were similar for the two regimens (52.1 percent for ciprofloxacin and 60.8 percent for doxycycline; p greater than 0.3) . However, in patients with chlamydial infections alone, ciprofloxacin was significantly less effective than doxycycline (45.5 percent versus 75 percent; p = 0.04) . In patients with U . urealyticum infections alone, there was a more favorable trend in the ciprofloxacin group (69.2 percent versus 45 percent; p = 0.12) . In patients whose culture results were negative, the responses were very similar (60.9 percent for ciprofloxacin and 64.3 percent for doxycycline) . Both drugs were well tolerated; side effects, which were mostly gastrointestinal in nature, were mild.

Am J Med, 1987 Apr 27, 82(4A), 242 - 6
Double-blind comparison of ciprofloxacin with cefotaxime in the treatment of skin and skin structure infections; Perez-Ruvalcaba JA et al.; Oral ciprofloxacin (750 mg twice daily) was compared with intravenous cefotaxime (2 g three times daily) as therapy for 61 episodes of skin and skin structure infections occurring in adult patients . A variety of infections including cellulitis, infected ulcers, abscesses, and other miscellaneous infections were treated . Clinical cure was achieved in 77 percent (24 patients) of 31 patients treated with ciprofloxacin and in 76 percent (22 patients) of 28 patients treated with cefotaxime . The response was slower in infected diabetic patients than in non-diabetic patients in both groups . Side effects were minimal and appeared only in the cefotaxime group . Ciprofloxacin taken twice daily was as effective as cefotaxime administered intravenously three times daily in the treatment of skin and skin structure infections.

Am J Med, 1987 Apr 27, 82(4A), 142 - 5
Pharmacokinetics of two dosage regimens of ciprofloxacin during a two-week therapeutic trial in patients with cystic fibrosis; Stutman HR et al.; Twenty-nine adult patients with cystic fibrosis received 750 or 1,000 mg of ciprofloxacin orally every 12 hours for two weeks . Pharmacokinetic data were collected on Days 1, 7, and 14 . Pharmacokinetic analyses revealed minor differences between the dosage regimens, and results were similar on the first, seventh, and last day of therapy . Means for peak serum concentration (3.1 to 5.0 micrograms/ml), elimination half-life (4.8 to 5.3 hours), area under the time-concentration curve, and serum clearance (36.8 to 44.5 liter/hour) were similar to previously reported results for patients without cystic fibrosis . Sputum concentrations approximated serum values.

Am J Med, 1987 Apr 27, 82(4A), 133 - 8
Penetration of ciprofloxacin into gynecologic tissues; Dalhoff A et al.; Penetration of ciprofloxacin into gynecologic tissues has been studied after administration of the following: a single oral dose of 500 mg; a single injection of 100 mg; single intravenous infusions of 200 mg and 300 mg, respectively; and repeated oral doses of 500 mg followed by an infusion of 200 mg . In general, tissue concentrations of ciprofloxacin exceeded the corresponding serum concentrations on average twofold to fivefold, irrespective of the route of administration or the size of the dose . For example, mean tissue and serum concentrations of ciprofloxacin determined 12 hours after administration of a single oral dose of 500 mg were as follows: serum, 0.09 mg/liter; ovary, 0.28 mg/kg; uterus, 0.49 mg/kg; endometrium, 0.23 mg/kg; myometrium, 0.34 mg/kg; and fallopian tube, 0.36 mg/kg . Repeated drug administration did not result in an accumulation of ciprofloxacin in either serum or the tissues studied.

Immunopharmacology, 1987 Apr, 13(2), 99 - 109
Effects of quinolones on interleukin 1 production in vitro by human monocytes; Roche Y et al.; The new quinoline derivative antibiotics (quinolones), pefloxacin and ciprofloxacin at concentrations higher than 50 micrograms/ml inhibit the PHA response of the human mononuclear leukocytes in vitro . Since monocytes have been shown to be accessory cells for the activation of lymphocytes by mitogens, we investigated the effects of pefloxacin and ciprofloxacin on extracellular interleukin 1 (IL-1) and cell-associated IL-1 from lipopolysaccharide-stimulated human monocytes . Pefloxacin and ciprofloxacin decreased the extracellular IL-1 in a dose-dependent manner, while cell-associated IL-1 was not altered . These effects were observed even after a short period of incubation (1 or 2 h) . No inhibitory activity against purified IL-1 or IL-2 could be demonstrated in the dialyzed supernatants from pefloxacin- or ciprofloxacin-treated monocytes . Neither pefloxacin nor ciprofloxacin modified the biological activity of preformed IL-1 . The decrease of extracellular IL-1 induced by pefloxacin and ciprofloxacin could, in part, account for the observed decrease in the proliferative response of human mononuclear leukocytes to phytohemagglutinin, as extracellular IL-1 and proliferative response were positively correlated (at various concentrations of pefloxacin and ciprofloxacin) . The decrease in extracellular IL-1 was not associated with any alteration in the expression of the HLA-DR antigen on the monocytes membrane . These data suggested that pefloxacin and ciprofloxacin could antagonize IL-1 production and release by lipopolysaccharide-stimulated monocytes . These quinolones could be interesting tools to study the production, processing, transport and release from the monocytes of IL-1.

J Clin Microbiol, 1987 Feb, 25(2), 456 - 7
Ability of ciprofloxacin but not pipemidic acid to differentiate all three biovariants of Mycobacterium fortuitum from Mycobacterium chelonae; Steele LC et al.; When tested against 312 clinical isolates of rapidly growing mycobacteria, the quinolone pipemidic acid correctly separated Mycobacterium chelonae (M . chelonei) from Mycobacterium fortuitum biovar fortuitum but not from biovar peregrinum or the third biovar complex . The new 4-quinolone ciprofloxacin correctly separated all three biovars of M . fortuitum from M . chelonae and appears to provide a better taxonomic test.

J Antimicrob Chemother, 1987 Feb, 19(2), 263 - 9
Effect of multiple dose oral ciprofloxacin on the pharmacokinetics of theophylline and indocyanine green; Nix DE et al.; Interaction between ciprofloxacin and theophylline was studied in eight male volunteers, who were randomly divided into two groups . All subjects were given intravenous theophylline and indocyanine green (ICG) on study days 0, 7 and 14 . Group I subjects received ciprofloxacin 750 mg orally every 12 h on days 1-7 . Group II subjects received ciprofloxacin 750 mg every 12 h on days 6-14 . No significant changes in ICG clearance or half-life were noted . A significant increase in theophylline half-life and volume of distribution was observed (P less than 0.05); however, clearance was not significantly decreased (P = 0.1) . A potentially clinically significant interaction was detected in three subjects whose theophylline clearance decreased by 42-113% . Until further clinical experience is gained, we advise caution when these agents are coadministered . Some adjustment in theophylline dosage may be required; therefore, these patients should have serum theophylline concentration measurements and careful clinical assessment for theophylline toxicity.

Chemioterapia, 1987 Feb, 6(1), 50 - 1
Oral ciprofloxacin in the treatment of uncomplicated gonococcal urethritis in men; De Lalla F et al.; Two hundred and seventy-one male patients suffering from uncomplicated gonococcal urethritis were treated in an open randomized study with either 250 mg (121 patients) or 500 mg (150 patients) single oral doses of ciprofloxacin . The efficacy of treatment was verified on the third day by direct examination of urethral swabs in 91 patients and by culture and direct microscopic examination in 180 subjects . Cure rates were 100% in the 500 mg group and 96.6% in the 250 mg treated patients . No side effects were seen . Ciprofloxacin appears to be a very effective and safe drug in the treatment of uncomplicated gonococcal urethritis in men.

J Med Microbiol, 1987 Feb, 23(1), 83 - 8
The response of Escherichia coli to ciprofloxacin and norfloxacin; Elliott TS et al.; The action of ciprofloxacin and norfloxacin on two strains of Escherichia coli was studied by diverse methods including electronmicroscopy, viable counting and continuous turbidimetric monitoring . During the first few hours of exposure to inhibitory concentrations of the drugs, the opacity of bacterial cultures continued to increase for a period that was inversely proportional to the drug concentration . This change corresponded to the appearance of filamentous bacteria, swollen forms and some lysis . There was subsequently a gradual drop in opacity during which extensive lysis occurred . As judged by viable counts of bacteria washed free of drug, cell death occurred within 30 min of first exposure to the drugs and continued over a 3-h period . Ultrastructure studies demonstrated that lysis was preceded by the formation of vacuoles, predominantly at the poles of the cells . At these sites, breaks in the cell walls eventually occurred, resulting in extrusion of the cytoplasmic contents.

Eur J Clin Pharmacol, 1987, 31(5), 589 - 93
Pharmacokinetics of ciprofloxacin tablets in renal failure; influence of haemodialysis; Singlas E et al.; The pharmacokinetics of ciprofloxacin has been studied after a single oral dose of 500 mg given to 5 normal subjects (N) and to 15 patients grouped according to their residual renal creatinine clearance: Group I, 8-30 ml X min-1, Group II, less than 8 ml X min-1, and Group III, haemodialysed patients studied twice--during an interdialysis period (IIIa) and in a 4 h haemodialysis session (IIIb) . Ciprofloxacin was assayed by reverse phase HPLC using a spectrofluorimetric detection . The peak plasma concentration (2-5 mg X l-1) was reached within 2 h after drug administration . Apparent volume of distribution, 6.6 (N), 5.0 (I), 2.7 (II) and 4.2 (IIIa) l X kg-1 and total plasma clearance, 770 (N), 440 (I), 378 (II) and 314 (IIIa) ml X min-1 were decreased in relation to the degree of renal impairment . Mean plasma half-lives for patients in the 4 groups were 7.3 (N), 10.4 (I), 7.2 (II) and 9.3 (IIIa) h . In groups N, I and II, 40, 16 and 8% of the administered dose was eliminated through the kidney, with mean renal clearances of 305 +/- 63, 61 +/- 21 and 21 +/- 3 ml X min-1 . A linear relationship was found between the renal clearance of ciprofloxacin and the glomerular filtration rate (r = 0.75, n = 15) . Ciprofloxacin was partly removed by haemodialysis (IIIb): the dialyser extraction ratio was 23% and the dialysis clearance was 40 ml X min-1.

Eur J Clin Pharmacol, 1987, 32(2), 217 - 8
Concentrations of ciprofloxacin in human liver, gallbladder, and bile after oral administration; Dan M et al.; We have measured concentrations of ciprofloxacin in serum, hepatic tissue, gallbladder, and bile in 10 patients after a single oral dose of 750 mg given before cholecystectomy . Mean liver and gallbladder tissue concentrations were 12.76 micrograms X g-1 +/- 2.79 (SEM) and 5.94 micrograms X g-1 +/- 1.35, respectively . Concentrations in bile taken from the gallbladder (7 patients) ranged from 68 to 225 micrograms X ml-1, with a mean bile/serum concentration ratio of 49 . Concentrations in bile taken from the common bile duct (2 patients) were 17 and 16 micrograms X ml-1.

Drugs, 1987, 34 Suppl 1, 21 - 5
Comparative pharmacokinetics of new quinolones; Lode H et al.; The pharmacokinetic properties of the new quinolones are characterised by a high volume of distribution, long biological half-life, low serum protein binding, elimination mainly by the kidneys, high total and renal clearances, limited biotransformation and a moderate to excellent bioavailability after oral administration . However, each quinolone derivative (ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin) possesses individual pharmacokinetic characteristics, which should be considered in the treatment of patients, especially when liver and/or renal dysfunction exists.

Drugs, 1987, 34 Suppl 1, 170 - 4
Interaction between quinolones and caffeine; Staib AH et al.; The effects of multiple doses of ofloxacin 200 mg, ciprofloxacin 250 mg or enoxacin 400 mg (all twice daily) on the pharmacokinetic properties of single doses of caffeine (220 to 230 mg) were investigated in 12 healthy volunteers . Intraindividual comparisons showed that ciprofloxacin and enoxacin significantly inhibited the elimination of caffeine . Ofloxacin, however, did not affect any of the measured pharmacokinetic properties of caffeine . Thus, caffeine should be avoided in patients with liver disorders, cardiac arrhythmias, latent epilepsy or in intensive care while undergoing treatment with enoxacin or ciprofloxacin.

Drugs, 1987, 34 Suppl 1, 159 - 69
Steady-state kinetics of the quinolone derivatives ofloxacin, enoxacin, ciprofloxacin and pefloxacin during maintenance treatment with theophylline; Wijnands WJ et al.; Some of the new quinolone derivatives may be of value in the treatment of respiratory tract infections . It has been demonstrated that enoxacin, pefloxacin and ciprofloxacin, but not ofloxacin, decreased the metabolic clearance of the bronchodilator theophylline . This resulted in elevated plasma theophylline concentrations and, in some of the patients, theophylline toxicity . When the pharmacokinetic parameters of enoxacin, pefloxacin, ciprofloxacin and ofloxacin obtained in the present study were compared with those obtained from other studies in healthy volunteers not given concomitant theophylline, there was no evidence of theophylline influencing the clearance of the investigated quinolones.

Eur J Clin Pharmacol, 1987, 33(4), 435 - 6
A clinically significant interaction between ciprofloxacin and theophylline; Thomson AH et al.; We report a case of theophylline toxicity following the co-administration of ciprofloxacin . Total theophylline clearance fell from 2.3 l.h-1 to 0.8 l.h-1 when ciprofloxacin was added to the treatment regimen and returned to 2.1 l.h-1 after ciprofloxacin was discontinued.

Chemotherapy, 1987, 33(6), 397 - 401
Ciprofloxacin penetration in pancreatic juice; Pederzoli P et al.; The penetration of ciprofloxacin in pancreatic juice was investigated in 5 patients with pancreatic fistula . The drug was administered as a single oral dose of 500 mg after which serial samples of pancreatic juice and serum were collected for ciprofloxacin assay . The following pharmacokinetic parameters (mean +/- SD) were estimated from the serum level versus time curves: clearance 11.51 +/- 2.85 (ml/min/kg); Vd area 3.08 +/- 1.20 ml/kg; terminal half-life 3.10 +/- 0.92 h; mean residence time 5.64 +/- 1.40 h . Ciprofloxacin serum levels declined rapidly after the third hour, whereas concentrations in pancreatic juice remained elevated (above 1 mg/1) for nearly 12 h . The pancreatic juice/serum ciprofloxacin concentration ratio increased gradually fom 0.63 +/- 0.45 after 0.5 h to 6.18 +/- 4.59 after 12 h (mean +/- SD) . Our data indicate that while the drug elimination half-life from the serum is short, the time-course of ciprofloxacin levels in the pancreatic juice conforms to a much slower disappearance rate . In particular, the ciprofloxacin levels achieved in pancreatic juice are constantly greater than the MICs of the bacteria generally responsible for pancreatic infections.

Br J Clin Pharmacol, 1986 Dec, 22(6), 677 - 83
The influence of quinolone derivatives on theophylline clearance; Wijnands WJ et al.; Enoxacin decreases the metabolic clearance of the bronchodilator theophylline not only in severely ill patients, but also in patients with stable chronic obstructive airways disease . In this comparative study, significantly increased plasma theophylline concentrations were measured during co-administration of enoxacin (110.9%) and, to a lesser degree, also during co-administration of pefloxacin (19.6%) and ciprofloxacin (22.8%) . Total body clearance of theophylline was significantly decreased by enoxacin (63.6%), ciprofloxacin (30.4%) and pefloxacin (29.4%) . The pharmacokinetic parameters of theophylline did not change during co-administration of ofloxacin and nalidixic acid . There is growing evidence that the observed interaction is caused not by the parent drugs, but by the 4-oxo metabolite of enoxacin, pefloxacin and ciprofloxacin.

J Antimicrob Chemother, 1986 Nov, 18 Suppl D, 175 - 8
Intravenous ciprofloxacin in the treatment of infection in immunocompromised patients; Wood ME et al.; We initially used ciprofloxacin to treat immunocompromised patients whose fever had failed to respond or had recurred in spite of multiple broad-spectrum antibiotics . Results in this group encouraged us to proceed with a randomized trial of ciprofloxacin plus benzylpenicillin versus our standard empirical regimen of netilmicin and piperacillin for the treatment of fever in immunocompromised patients . Although the numbers of patients in this study are at present too small for comparison to be made, the favourable results seen in the refractory treatment group appear to be borne out so far in those receiving ciprofloxacin as first-line therapy.

J Antimicrob Chemother, 1986 Nov, 18 Suppl D, 187 - 93
Ciprofloxacin: an overview of adverse experiences; Ball P; This review summarizes adverse reactions probably or possibly attributable to oral ciprofloxacin therapy in worldwide clinical experience involving over 6500 patients . In Europe and Japan the overall incidence of adverse reactions amongst patients receiving ciprofloxacin is reported to be 3.0% and 6.5%, respectively . An increased incidence (13.4%) has been reported from the U.S.A., possibly relating to the use of higher dosages . Very few reactions have necessitated withdrawal of treatment . The most common adverse effects involve the gastro-intestinal system (2-8% of patients treated) and usually comprise nausea, vomiting, diarrhoea and abdominal discomfort . CNS effects are seen in 1-4% of patients but are usually minor dizziness or mild headache only . Hypersensitivity reactions, most commonly skin rashes or pruritus, affect about 1% of patients . There is little evidence of significant haematological or biochemical toxicity, other than a few reports of transient neutropenia and the finding, in a minority of clinical studies, of equally transient, usually trivial and invariably reversible elevations of serum aminotransferases . Serious, ciprofloxacin-related toxicity has been observed in only three patients: one who developed pseudomembranous colitis, another who developed interstitial nephritis and a third who had a grand-mal convulsion during concomitant administration of theophylline . Ciprofloxacin appears to have an excellent safety profile.

Arzneimittelforschung, 1986 Oct, 36(10), 1503 - 10
Pharmacokinetics of ciprofloxacin . 2nd communication: distribution to and elimination from tissues and organs following single or repeated administration of {14C}ciprofloxacin in albino rats; Siefert HM et al.; 1-Cyclopropyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-{U-14C}piperazinyl)-3-quinoline carboxylic acid (ciprofloxacin, Bay o 9867; designated tradename: Ciprobay) was administered to male and to pregnant albino rats with single intravenous or oral doses of 5 or 10 mg/kg body weight and with repeated oral doses of 5 mg/kg (7 consecutive daily administrations to male rats) . Following a single intravenous administration the {14C}ciprofloxacin related radioactivity was distributed rapidly and differentiated to the body . Compared to plasma high concentrations were determined in kidney, liver, skeleton muscle, pancreas, testes and cartilage, low concentrations occurred in brain and adipose tissue . In some selected tissues radioactivity was largely due to unchanged {14C}ciprofloxacin (57% to 100%) . A good penetration of total radioactivity into tissues and organs with a similar distribution pattern as detected after intravenous dosing also occurred after a single oral administration . Highest concentrations were determined 1 h after dosing . Compared to plasma most tissues and organs showed higher concentrations and higher AUC-values . For brain and eye low values were determined . Compared to plasma a longer mean residence time of radioactivity was calculated for brain, eye, eye-wall, testes and blood cells . 6 d after single administration the radioactive residues in the body exclusive gastrointestinal tract amounted to less than 0.1% of the dose . Following a seven-day treatment the distribution pattern of total radioactivity in the body did not differ essentially from that after single dosing . Compared to single dosing AUC-values higher by the factor 2 to 4 were calculated after repeated administration for plasma and most of the tissues and organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1986 Sep, 262(3), 396 - 402
Effects of ciprofloxacin on the humoral and cellular immune responses in Balb/c-mice; Roszkowski W et al.; The effects of a 7 days chemotherapy with ciprofloxacin on the humoral and cellular immune responses in Balb/c-mice were examined . Ciprofloxacin-doses used were calculated on a body weight basis from therapeutic dosages in humans . In a dose-dependent way IgM as well as IgG responses were significantly increased . The delayed-type hypersensitivity reaction to oxazolone was not significantly changed . In in vivo as well in vitro experiments ciprofloxacin showed no modulatory activity on the concanavalin A and LPS-induced proliferative activities of mouse spleen cells.

Antimicrob Agents Chemother, 1986 Sep, 30(3), 444 - 6
Absolute oral bioavailability of ciprofloxacin; Drusano GL et al.; We evaluated the absolute bioavailability of ciprofloxacin, a new quinoline carboxylic acid, in 12 healthy male volunteers . Doses of 200 mg were given to each of the volunteers in a randomized, crossover manner 1 week apart orally and as a 10-min intravenous infusion . Half-lives (mean +/- standard deviation) for the intravenous and oral administration arms were 4.2 +/- 0.77 and 4.11 +/- 0.74 h, respectively . The serum clearance rate averaged 28.5 +/- 4.7 liters/h per 1.73 m2 for the intravenous administration arm . The renal clearance rate accounted for approximately 60% of the corresponding serum clearance rate and was 16.9 +/- 3.0 liters/h per 1.73 m2 for the intravenous arm and 17.0 +/- 2.86 liters/h per 1.73 m2 for the oral administration arm . Absorption was rapid, with peak concentrations in serum occurring at 0.71 +/- 0.15 h . Bioavailability, defined as the ratio of the area under the curve from 0 h to infinity for the oral to the intravenous dose, was 69 +/- 7% . We conclude that ciprofloxacin is rapidly absorbed and reliably bioavailable in these healthy volunteers . Further studies with ciprofloxacin should be undertaken in target patient populations under actual clinical circumstances.

Antimicrob Agents Chemother, 1986 Sep, 30(3), 440 - 3
Dose ranging study and constant infusion evaluation of ciprofloxacin; Drusano GL et al.; We evaluated the pharmacokinetics of 100- and 200-mg doses of ciprofloxacin, with the 200-mg dose administered either as a 30-min infusion or as a 100-mg loading dose followed by a 4-h constant infusion of 25 mg/h in six normal volunteers . No significant differences were seen in the dose-normalized area under the curve when the 100- and 200-mg 30-min administrations were compared . Differences that approached statistical significance were seen when data from either of these trials were compared with data from the constant-infusion arm . Serum clearances averaged 23.0 +/- 9.1 liters/h per 1.73 m2 for the 100-mg dose and 23.7 +/- 5.1 liters/h per 1.73 m2 for the 200-mg dose . Renal clearance accounted for approximately two-thirds of the serum clearance in each instance . Half-lives were slightly longer than 4 h . For the constant-infusion arm, serum clearance was 28.9 +/- 2.7 liters/h per 1.73 m2, with renal clearance accounting for 58% of serum clearance . Although no nonlinearities were apparent in the 100- to 200-mg dose range, larger doses, particularly in the multiple-dosing situation, may uncover nonlinearity in the disposition of ciprofloxacin.

Arzneimittelforschung, 1986 Jul, 36(7), 1144 - 7
{The effect of ciprofloxacin on epinephrine and collagen-induced thrombocyte aggregation in vitro}; Reuter HD et al.; Concentrations of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid (ciprofloxacin; designated tradename: Ciprobay) similar to maximal levels obtained in the serum of patients with intact renal function after application of therapeutic doses and 4- to 5-fold such concentrations do not influence epinephrine- or collagen-induced aggregation . 100 micrograms/ml ciprofloxacin, corresponding to the 20 fold maximal serum level of patients with intact renal function, does not influence aggregation induced by 2 micrograms/ml collagen as regards degree and kinetics of aggregation, while aggregation induced by 0.2 micrograms/ml collagen is significantly reduce . Aggregation induced by 1, 2 and 4 mumol/l epinephrine is also reduced significantly by 100 micrograms/ml ciprofloxacin . Changes brought about by high doses of ciprofloxacin still occur within the normal range . It is therefore concluded from this study that the hemostatic function of the platelets is not influenced in a clinically relevant manner by ciprofloxacin . Regarding the effect on platelet aggregation ciprofloxacin corresponds to the structurally related pipemidic acid.

Infection, 1986 Jul-Aug, 14(4), 190 - 4
Comparative therapeutic activities of ciprofloxacin, amoxicillin, ceftriaxone and co-trimoxazole in a new model of experimental infection with Escherichia coli; Hof H et al.; A new mouse model for systemic infection with Escherichia coli is presented . Whereas in other models 10(7)-10(8) bacteria have to be injected into an animal to induce toxic effects resulting in death within 24 hours, now, only 10(3)-10(4) bacteria of an appropriate strain are required to produce a genuine infection characterized by an increase in the bacterial load over several days . The quantitative determination of bacterial counts per liver allows a more sensitive measurement than recording death rates . Furthermore, few animals are required for a definite result in contrast to the LD50 determination of other models . The salient point regarding this new model is that conditioning of animals has to be achieved by incorporating the inoculum into agar which is injected subcutaneously . The resulting infection is completely dependent on the E . coli strain used . Whereas a hemolytic, uropathogenic strain is so virulent that an overwhelming infection develops within 48 hours after the injection of 10(3) bacterial cells, a non-hemolytic variant of this strain is completely avirulent, being unable to multiply in spite of the potentiating agar . The hemolytic E . coli strain ATCC 25922 is intermediate in virulence . The bacterial counts per liver increase steadily until death occurs five to seven days after the injection of 10(4) bacteria . This bacterial infection can be therapeutically influenced by daily treatment with various drugs . Ciprofloxacin, ceftriaxone and co-trimoxazole are able to cure the infection, whereas amoxicillin given orally is only moderately active against this ATCC strain, which is relatively resistant to amoxicillin.

Antimicrob Agents Chemother, 1986 Jul, 30(1), 172 - 3
Susceptibility of Eikenella corrodens to newer and older quinolones; Goldstein EJ et al.; The susceptibilities of 44 clinical strains and a reference strain (ATCC 23834) of Eikenella corrodens were determined by agar dilution . All isolates were very susceptible (MICs, less than 2 micrograms/ml) to amifloxacin, ciprofloxacin, difloxacin, enoxacin, norfloxacin, ofloxacin, and Win 35439.

J Antimicrob Chemother, 1986 Jul, 18(1), 107 - 12
Pharmacokinetics of single dose intravenous ciprofloxacin in patients undergoing gastrointestinal surgery; Silverman SH et al.; The pharmacokinetics of single dose intravenous ciprofloxacin in patients undergoing gastrointestinal surgery (100 mg, n = 8; 200 mg n = 18) have been studied . Following 100 mg therapeutic serum levels were maintained for approximately 40 min only and tissue concentrations were frequently less than 0.15 mg/kg . 200 mg maintained therapeutic serum levels for at least 150 min and produced mean concentrations in fat, muscle, peritoneum and gut wall of 1.04, 1.94, 1.59, and 3.39 mg/kg respectively . 200 mg iv ciprofloxacin would appear to provide adequate serum and tissue concentrations for at least 150 min.

Antimicrob Agents Chemother, 1986 Jul, 30(1), 184 - 6
Comparative efficacy of ciprofloxacin and ceftriaxone in experimental arthritis caused by Escherichia coli; Bayer AS et al.; Ciprofloxacin was compared with ceftriaxone in a rabbit model of septic arthritis caused by Escherichia coli . Both agents significantly reduced mean E . coli counts in septic joint fluid (P less than 0.0005 versus untreated controls) and also within infected synovial tissue (P less than 0.01 versus controls) . Ciprofloxacin regimens caused a higher frequency (P less than 0.05) of synovial tissue sterilization (53%) than did ceftriaxone (25%).

Immun Infekt, 1986 Jul, 14(4), 152 - 5
{Ciprofloxacin and cefotaxim: pharmacokinetic and therapeutic effectiveness in E . coli pyelonephritis in rats}; Tietgen K et al.; Ciprofloxacin was tested in the acute and chronic experimental E.coli pyelonephritis in rats . Its therapeutic efficacy was compared with that of cefotaxime . In the acute pyelonephritis increasing doses resulted in increasing elimination of bacteria from the kidneys . Ciprofloxacin and cefotaxime showed no difference in the efficiency in therapy of the acute pyelonephritis . In chronic pyelonephritis ciprofloxacin proved to be more effective than cefotaxime in spite of identical in vitro activity . Pharmacokinetic data showed that ciprofloxacin was eliminated more slowly than cefotaxime . The long serum half-life and the high volume of distribution could be responsible for the high therapeutic efficacy and could outweigh the disadvantage of metabolic instability.

Antimicrob Agents Chemother, 1986 Jun, 29(6), 1088 - 9
Ciprofloxacin in the treatment of pneumonia; Ernst JA et al.; The use of ciprofloxacin as the sole agent in the treatment of 25 patients with pneumonias caused by susceptible organisms resulted in rapid cure . No side effects, superinfections, or recurrences were observed.

Eur J Clin Microbiol, 1986 Apr, 5(2), 244 - 6
Treatment of uncomplicated gonococcal urethritis in men with two dosages of ciprofloxacin; Tegelberg-Stassen MJ et al.; One hundred and sixty-four male patients suffering from urethral gonorrhoea were treated in an open randomised trial with either 250 mg (n = 85) or 500 mg (n = 79) ciprofloxacin administered in one tablet . Cure rates in both groups were 100% . Postgonococcal urethritis was observed in 31 of 85 (36%) patients in the first group, and in 21 of 79 patients (27%) in the second group . Side-effects were minor, occurring in four patients in the 250 mg group (4.7%) and in seven in the 500 mg group (8.9%) . The side-effects consisted of nausea, diarrhoea and headache . Ciprofloxacin would appear to be a very effective drug in the treatment of urethral gonorrhoea in males.

Antimicrob Agents Chemother, 1986 Mar, 29(3), 506 - 8
Quinolones affect thymidine incorporation into the DNA of human lymphocytes; Forsgren A et al.; The incorporation of {3H}thymidine into DNA was increased in phytohemagglutinin-stimulated human lymphocytes exposed to four of the new quinolone derivatives (ciprofloxacin, norfloxacin, ofloxacin, and A 56620) at concentrations achievable in clinical situations . However, proliferation of phytohemagglutinin-stimulated lymphocytes was not influenced by ciprofloxacin at concentrations of 0.5 to 10 micrograms/ml.

Antimicrob Agents Chemother, 1986 Mar, 29(3), 424 - 5
In vitro susceptibility of Rickettsia conorii to ciprofloxacin as determined by suppressing lethality in chicken embryos and by plaque assay; Raoult D et al.; We tested the susceptibility of Rickettsia conorii to ciprofloxacin, a new quinolone antibiotic . A final concentration of 1 microgram/g of egg was effective in suppressing chicken embryo lethality, and a concentration of 0.25 micrograms/ml inhibited plaque formation in a plaque assay; however, a concentration of 0.5 microgram/ml was necessary to obtain rickettsiacidal activity . These results support the idea that ciprofloxacin could be of clinical use in treating Mediterranean spotted fever.

Antimicrob Agents Chemother, 1986 Mar, 29(3), 386 - 8
Comparative in vitro activities of ciprofloxacin and other 4-quinolones against Mycobacterium tuberculosis and Mycobacterium intracellulare; Fenlon CH et al.; The in vitro activity of ciprofloxacin, ofloxacin, amifloxacin, and norfloxacin against 22 clinical isolates of Mycobacterium tuberculosis was evaluated by agar dilution . The MICs for 90% of the isolates of ciprofloxacin and ofloxacin were 0.5 and 1 microgram/ml, respectively . Amifloxacin and norfloxacin were less active . The MICs for 90% of the isolates of ciprofloxacin and ofloxacin against 20 clinical isolates of Mycobacterium intracellulare were determined by agar dilution to be 2 and 8 micrograms/ml, respectively.

Pharmacotherapy, 1986 Mar-Apr, 6(2), 87 - 91
Pharmacokinetics of ciprofloxacin in elderly subjects; LeBel M et al.; The pharmacokinetics of single-dose oral ciprofloxacin 500 mg was ascertained in 12 elderly and 12 young subjects . Mean age of the elderly volunteers was 75.4 years and the mean measured creatinine clearance in this group was 40.7 ml/min . Serum and saliva were collected in serial order for 24 hours (elderly) and 10 hours (young), and assayed for ciprofloxacin by high-performance liquid chromatography . The geriatric subjects had higher serum levels throughout the sampling period, with a peak level of 3.24 +/- 0.79 versus 2.26 +/- 0.75 micrograms/ml for the younger group (p less than 0.005; one-way analysis of variance) . A twofold increase in the ciprofloxacin half-life may be partly explained by a decrease in the glomerular filtration rate, as shown by slower ciprofloxacin renal clearance (152.4 +/- 54.2 vs 395.6 +/- 139.0 for elderly and young subjects respectively; p less than 0.001) . We concluded that in elderly patients, ciprofloxacin should be administered at an interval not less than every 12 hours to prevent accumulation and eventually toxicity.

Pharm Weekbl Sci, 1986 Feb 21, 8(1), 63 - 6
Ciprofloxacin in oral treatment of ear infections; Van de Heyning PH et al.; In a pilot study 29 cases of suppurative otitis were treated with ciprofloxacin . Acceptable clinical results were obtained in case of chronic otitis media without cholesteatoma and in case of otitis externa . Cholesteatoma and mastoid cavity cases gave no satisfactory results . Guidelines are proposed to define the specific indications and place of this drug in suppurative otitis.

Pharm Weekbl Sci, 1986 Feb 21, 8(1), 35 - 9
Pharmacokinetics of intravenously administered ciprofloxacin in intensive care patients with acute renal failure; Dirksen MS et al.; The pharmacokinetics of ciprofloxacin after a single intravenous administration of 100 mg were studied in intensive care patients with an acute renal impairment . There was no correlation found between the creatinine clearance and the renal clearance of ciprofloxacin . This applies to the entire group of patients . The decrease in renal clearance of ciprofloxacin was, however, more pronounced than the change in the elimination half-life, suggesting an important extra-renal elimination of the drug.

Antimicrob Agents Chemother, 1986 Feb, 29(2), 337 - 8
Effect of ciprofloxacin on mitogen-stimulated lymphocyte proliferation; Gollapudi SV et al.; Ciprofloxacin was tested for its inhibitory or stimulatory effects on concanavalin A- and phytohemagglutinin-stimulated proliferation (measured by {3H}thymidine uptake) of human peripheral blood mononuclear cells and murine splenocytes . Ciprofloxacin did not diminish or enhance mononuclear cell proliferation at concentrations of 5 to 125 micrograms/ml . Further, the proliferative response of splenocytes of mice previously treated with ciprofloxacin (40 mg/kg, twice daily for 5 days) was essentially similar to that of untreated controls.

Chemotherapy, 1986, 32(5), 468 - 72
Effect of ciprofloxacin on stationary bacteria studied in vivo in a murine granuloma pouch model infected with Escherichia coli; Zeiler HJ et al.; A granuloma pouch model in mice was used to investigate the effect of ciprofloxacin in vivo on cells of Escherichia coli (Neumann) under stationary growth conditions . The animals were treated up to three times intraperitoneally with 2.5, 10 or 40 mg/kg ciprofloxacin 24 h after infection . The numbers of viable bacteria in the pouch exudate were determined over a period of 24 h . A rapid decline of more than 1 logarithmic unit of the number of colony forming units was observed after 2-4 h with all treatment schedules . The effect on stationary cells was more pronounced with the high dose of ciprofloxacin and also dependent on the frequency of treatment . Ciprofloxacin penetrated well into the pouch exudate and reached concentrations of 2.08 +/- 0.16 microgram/ml and 0.1 +/- 0.05 microgram/ml 2 h after treatment with 40 and 2.5 mg/kg, respectively . The results of this study demonstrate that ciprofloxacin is effective in the treatment of a local inflammatory abscess in mice harbouring a stationary population of E . coli.

Graefes Arch Clin Exp Ophthalmol, 1986, 224(6), 502 - 6
Investigations on rat eyes with diabetic cataract and naphthalene cataract by Zeiss-Scheimpflug measuring system SLC; Hockwin O et al.; Experimental cataract development can be objectively monitored in rats by Scheimpflug slit-image photography and microdensitometric image analysis . Zeiss (Oberkochen, Federal Republic of Germany) has developed a new computerized slit-lamp measuring system that works according to the Scheimpflug principle; we have very successfully applied it to rats with streptozotocin-induced cataracta diabetica vera and with naphthalene-induced opacities . With these cataract models we tested the gyrase inhibitor compound, Ciprofloxacin (Bayer 09867), after 6 weeks' daily peroral application (20 mg/kg body weight) for differences in cataract progression indicating a possible cocataractogenic effect of the compound . When we compared the two different Scheimpflug methods, we found that the Zeiss-Scheimpflug measuring system SLC has some handling advantages with respect to animal cataract studies . If the equipment is to be fully used, complements to the program of the integrated computer part are necessary . The image-analytical results from the animals treated with Ciprofloxacin did not show any indication of cocataractogenic potential with respect to cataracta diabetica vera or naphthalene cataract.

Chemotherapy, 1986, 32(1), 7 - 17
Penetration of ciprofloxacin into gynecological tissues following oral and intravenous administration; Goormans E et al.; Penetration activities of ciprofloxacin into female genital tract tissues were studied following a single oral administration of 500 mg and an intravenous injection of 100 mg . Serum and tissue concentrations were within the same order of magnitude 1 and 3 h after oral administration; 3 h after intake of ciprofloxacin, however, tissue concentrations exceeded the corresponding serum levels twofold . Similarly, tissue concentrations following intravenous injection exceeded the corresponding serum levels by 60-190% 0.5 h after injection and were consistently higher throughout the study period of 2 h . These data confirm that ciprofloxacin disposition is characterized by a remarkably pronounced diffusion into the extravascular space, generating tissue levels exceeding the minimal inhibitory concentrations of most pathogens severalfold.

J Hyg (Lond), 1985 Dec, 95(3), 619 - 21
Differentiation of Mycobacterium chelonei from M . fortuitum by ciprofloxacin susceptibility; Collins CH et al.; Seventy-five strains of Mycobacterium fortuitum were inhibited by 3.0 mg/l ciprofloxacin but 36 strains of M . chelonei were resistant . The results correlated well with those obtained by the nitratase test . The ciprofloxacin sensitivity test is a useful supplement to the tests used to identify these two species.

Infection, 1985 Mar-Apr, 13(2), 78 - 81
Tissue distribution of ciprofloxacin following oral and intravenous administration; Dalhoff A et al.; Ciprofloxacin distribution in muscle, subcutaneous fat and perirenal and perivesical fat was studied following a single i.v . bolus injection of 100 mg or oral administration of 500 mg . Levels in muscle were on average 0.75 mg/kg; diffusion into muscle was rapid, whereas elimination from muscle was slow . Similar peak levels were recorded in fatty tissues . However, penetration into subcutaneous fat in particular may be delayed in individual cases . Following an initial lagphase of up to one hour after i.v . injection, ciprofloxacin distribution was as efficient in these patients as in the others . Tissue levels following oral administration were monitored 12 hours after intake . On average, ciprofloxacin concentrations in serum, muscle and perirenal fat were 0.17 mg/l, 0.20 mg/kg and 0.11 mg/kg, respectively . Thus, ciprofloxacin is distributed effectively throughout the extravascular space following i.v . as well as oral administration.

Chemotherapy, 1985, 31(1), 13 - 8
Ciprofloxacin distribution in prostatic tissue and fluid following oral administration; Boerema JB et al.; The penetration of ciprofloxacin into prostatic tissue was studied following oral administration of 500 mg either once or repeatedly in 12-hourly intervals . Following single administration ciprofloxacin was rapidly absorbed from the gastrointestinal tract peaking 1-2 h after administration . Elimination from serum was slow, the half life being 4.3 h . No significant rise in serum concentrations was noticed following repeated administration . Ciprofloxacin was concentrated in the prostatic tissue, levels being on average twice as high as the corresponding serum concentrations . The ratios between prostate and serum levels following single and repeated administration were 227 and 214%, respectively . Intraindividual analysis of prostate concentrations in different areas of the prostatic gland revealed a homogeneous distribution within the prostate . Penetration of ciprofloxacin into prostatic fluid was studied in 11 patients 2-4.5 h after administration . At these points ratios between prostatic fluid and serum ranged between 1.5 and 450%.

Infection, 1984 Sep-Oct, 12(5), 355 - 7
Ciprofloxacin concentrations in tonsils following a single intravenous infusion; Falser N et al.; Penetration of ciprofloxacin into human tonsils was studied following an intravenous infusion of 200 mg over 15 minutes to adult humans undergoing tonsillectomy . Samples were taken one-and-a-half to four hours after dosing . Generally, tissue levels exceeded corresponding serum concentrations by 50% (range of intraindividual ratios between tonsil and serum concentrations 100% to 288%) . Ciprofloxacin distribution was homogeneous and independent of sampling time.

Clin Pharmacol Ther, 1984 Sep, 36(3), 384 - 8
Multiple-dose ciprofloxacin kinetics in normal subjects; Aronoff GE et al.; To determine multiple-dose kinetics of the quinoline carboxylic acid derivative ciprofloxacin, we gave 12 normal subjects ciprofloxacin, 250 mg by mouth every 12 hr for 13 doses . Plasma concentrations were measured by HPLC after the first, seventh, and thirteenth doses . Peak and trough plasma concentrations were measured daily . Ciprofloxacin was rapidly absorbed from the gastrointestinal tract and reached maximum serum concentrations about 1 hr after dosing . Ciprofloxacin elimination t1/2 increased from 3.71 hr after the first dose to 6.51 hr after the thirteenth dose (P less than 0.05) . Apparent plasma clearance decreased from 0.823 to 0.629 l/kg/hr because of decreased nonrenal clearance . Drug cumulation did not occur throughout the experiment . We conclude that concentrations of ciprofloxacin in excess of the minimum inhibitory concentrations for many important pathogens can be achieved in plasma and that controlled clinical trials of ciprofloxacin efficacy in selected systemic infections are warranted.

Eur J Clin Microbiol, 1984 Aug, 3(4), 360 - 2
Diffusion of ciprofloxacin into prostatic fluid; Dalhoff A et al.; To determine whether ciprofloxacin might be efficacious in therapy for chronic bacterial prostatitis, its diffusion into prostatic fluid was studied in ten healthy volunteers . One hour after administering 500 mg ciprofloxacin, the concentration of ciprofloxacin was measured by the agar diffusion method and bioassay . Serum levels were twice as high as in seminal fluid; however, 12 and 24 hours later concentration in seminal fluid was tenfold higher than in serum . Split ejaculates were examined to determine the secretory pattern of ciprofloxacin into seminal fluid . The two fractions also showed tenfold concentration . Ciprofloxacin concentration in expressed prostatic secretion ranged from 15 to 0.9 mg/l, thus indicating pronounced diffusion of ciprofloxacin into the prostatic fluid.

Antimicrob Agents Chemother, 1984 Jul, 26(1), 94 - 6
In vitro activities of norfloxacin and ciprofloxacin against Mycobacterium tuberculosis, M . avium complex, M . chelonei, M . fortuitum, and M . kansasii; Gay JD et al.; The activities of ciprofloxacin and norfloxacin against 100 mycobacteria isolates were studied in vitro by the 1% standard proportion method . Ciprofloxacin was more active against M . tuberculosis and M . fortuitum with MICs of 1.0 and 0.25 microgram/ml, respectively, against 90% of isolates; norfloxacin had MICs of 8.0 and 2.0 micrograms/ml, respectively, against 90% of isolates.

What Is Cell Biology?, What Is Biofilm?, What Is Pcr?, What Is Staphylococcus Aureus?, What Is Biofilter?, r, Microorganisms, r, Microorganism, n, Bacteria, e, Bacterium, n, Bacteriology, r, Yeasts, s, Biofilms, s, Antimicrobials, o, Lactobacillus, o, Agrobacterium, e, S. cerevisiae, a, Cell suspensions, e, Streptococci, n, Streptococcal, s, Streptococcal, i, Amikacin, o, S. cerevisiae, a, Escherichia coli, s, Yeasts, r, Biofilms, r, Bacteria, i, Escherichia coli, a, Microbial, r, Streptococcal, r, Vibriosis, s, Staphylococcus

Scientific Publications - Work Done by Microbiology Reader Bioscreen C
Agricultural Microbiology Anaerobic Microbiology Antimicrobial Susceptibility Artificial Atmosphere Bioassay of Antibiotics Biofilm Microbiology Bioreactor Technology Biotechnology Cell Biology Clinical Microbiology Environmental Microbiology Experiments with Yeast	Fermentation Food Microbiology Functional Genomics Gene Technology Growth Media Development Growth Rate and Lag Time Industrial Microbiology Medical/Pharmaceutical Field Microbiological Assay Microbiological Research Microbiology of Cosmetics go to a specific theme...	Military Microbiology Molecular Microbiology Mutagenicity and Genotoxicity Oral Microbiology Patents Postantibiotic Studies Soil Microbiology Spore Microbiology Veterinary Microbiology Waste/Wastewater Treatment Water Microbiology Wine Microbiology

� 2005 Transgalactic Ltd (manufacturer of Bioscreen C software) | Privacy Statement | P.O. Box 1393, 00101 Helsinki, Finland, phone: +358 9 85172920, fax: +358 9 8749481, e-mail: microbiology@bionewsonline.com

Last modified: May 25, 2005