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