Pharmacol Toxicol, 1992 Nov, 71(5), 348 - 52 Interaction between ciprofloxacin and thiopental in the central nervous system of the male rat; Schliamser SE et al.; The effect of intravenous ciprofloxacin (CPX) pretreatment on the kinetics and brain sensitivity for thiopental was studied in male rats using a previously developed electroencephalographic (EEG) threshold method . Thiopental was administered intravenously with constant infusion rate . Immediately after the appearance of the first burst suppression of 1 sec . or more (the "silent-second") in the EEG the infusion was stopped and the rats were killed by decapitation . The dose of thiopental needed to reach the criterion of silent-second was slightly reduced in ciprofloxacin pretreated rats when compared with saline pretreated controls . One rat that developed seizures after CPX pretreatment needed a considerably reduced dose of thiopental to induce the silent-second . The serum concentrations of thiopental were markedly reduced in the experimental group while no significant differences were found in the concentrations of thiopental in the different parts of the central nervous system (CNS), fat or muscle tissue . The kinetics of CPX were also affected . The experimental group (CPX + thiopental treated) had significant higher brain concentrations of CPX than the corresponding only CPX treated control group while no differences were found in the serum concentrations of CPX between the groups . As previously suggested, the distribution of thiopental in the CNS is not only dependent on its lipid solubility, but also as a weak organic acid, on the transport system for organic acids out of the CNS which both thiopental and ciprofloxacin seem to use and mutually compete for it. Infection, 1992 Nov-Dec, 20(6), 324 - 7 Transintestinal elimination of ciprofloxacin in humans--concomitant assessment of its metabolites in serum, ileum and colon; Viell B et al.; Ciprofloxacin (200 mg) was infused to seven patients at the beginning of elective colorectal surgery . Thirty minutes after the end of infusion (i.e . 60 min after the start of the operation) ciprofloxacin reached concentrations of 1.60 mg/l in serum and of 3.42-6.07 mg/kg fresh weight in the ileum and colon . During the next 30 min (90 min after the start of operation) the concentration of ciprofloxacin in serum decreased to 86% of its initial level, but this decrease was less rapid than that observed in the ileal (to 56.8%) or colonic (to 74.8%) mucosa . Three metabolites could be identified (desethylen-, sulpho-, oxociprofloxacin) . Initially, at 60 min the amount of these metabolites was about 15% of the total drug concentration in serum, but only 2-3% of that in the gut tissues . At 90 min the relative amount of metabolites was increased in serum as well as in the gut tissues . It is concluded that transintestinal elimination of ciprofloxacin is a general feature of the whole gut . Obviously, the elimination process is not due to degradation of ciprofloxacin within the gut wall. Trans R Soc Trop Med Hyg, 1992 Nov-Dec, 86(6), 590 - 7 The effects of multiplication and synchronicity on the vascular distribution of parasites in falciparum malaria; White NJ et al.; The sequestration of erythrocytes containing mature forms of Plasmodium falciparum in the microvasculature of vital organs may cause large discrepancies between the peripheral blood parasite count and the total body parasite burden in falciparum malaria . Despite this, parasitaemia is widely used as an indicator of prognosis and response to treatment . A simple mathematical model describing the changes in circulating and sequestered parasite numbers during acute falciparum malaria is presented . The model uses two parameters only; the standard deviation (SD) of parasite age since merogony (schizogony) as as a measure of synchronicity, and a multiplication factor each 48 h asexual life cycle . The model predicts that during the rising phase of the infection the ratio of circulating to sequestered parasites is dependent largely on the synchronicity of infection rather than multiplication rate, and that in synchronous infections parasitaemias will show considerable fluctuation when the mean stage of parasite development is in the second half of the asexual life cycle . The model fitted well to serial parasite counts from 4 patients with acute uncomplicated falciparum malaria whose infections failed to respond to ciprofloxacin . All four infections were synchronous (SD < or = 4 h), and showed large fluctuations in parasitaemia over short periods related to synchronous sequestration and subsequent reinvasion following merogony . The parasite multiplication rate was determined mainly by the efficiency of merogony or merozoite invasion rather than clearance of circulating parasitized erythrocytes . This suggests that the spleen is relatively inactive during the rising phase of the infection . Quinine treatment did not prevent sequestration but did stop subsequent multiplication.(ABSTRACT TRUNCATED AT 250 WORDS) Can J Ophthalmol, 1992 Oct, 27(6), 277 - 82 Toxicity and pharmacokinetics of intravitreally injected ciprofloxacin in rabbit eyes; Rootman DS et al.; To assess the toxicity of intraocular injection of ciprofloxacin, 22 New Zealand white rabbits received midvitreal injections of 100, 200, 400, 800 or 3200 micrograms of ciprofloxacin in 0.1 mL of distilled water (39 eyes) or 0.1 mL of distilled water only (5 eyes) . The ocular pharmacokinetics of intravitreally injected ciprofloxacin was determined by aqueous humour and vitreous sampling 1, 2, 4, 8, 12, 18 or 24 hours after midvitreal injection of 100 micrograms of the drug in one eye each of 25 New Zealand white rabbits . The samples were analysed by means of a disc diffusion bioassay . No ocular damage was noted on ophthalmoscopy at any of the concentrations tested . Histologic study showed mild, transient vacuolation of the nerve-fibre layer in all eyes, including the control eyes, 2 hours after injection; at 24 hours no vacuolation was evident except at concentrations of 800 and 3200 micrograms, at which plexiform layer damage was evident . Peak aqueous and vitreous levels of ciprofloxacin were obtained at 1 hour (0.59 and 27.26 micrograms/mL respectively); the vitreous level fell to below 1.0 micrograms/mL 12 hours after injection . We conclude that intravitreally injected ciprofloxacin may be a safe and useful antibiotic in the treatment of aminoglycoside-resistant bacterial endophthalmitis. Dtsch Med Wochenschr, 1992 Sep 18, 117(38), 1434 - 8 {Rhinocerebral mucormycosis during deferoxamine therapy}; Ammon A et al.; A 24-year-old woman had been in full remission of an acute myeloid leukaemia since 1988, but she required regular erythrocyte and platelet transfusions for pancytopenia . To counteract a progressive siderophilia due to the transfusions (ferritin levels of about 10,000 ng/ml) deferoxamine was intermittently given intravenously (5 g after each transfusion) . Seven months after the start of this treatment the patient was hospitalized because of severe left-sided facial pain as well as reddening and swelling in the periorbital region . As maxillary and frontal sinusitis was suspected, antibiotics were administered (at first three times daily 2.2 g amoxicillin and clavulanic acid, then two times daily 300 mg rifampicin and 200 mg ciprofloxacin) . Nonetheless, orbital phlegmon developed within a few days with protrusion and blindness of the left eye necessitating a decompression operation . Material obtained at operation revealed rhinocerebral mucormycosis . After 3 weeks of antimycotic treatment with both amphotericin B (1 mg/kg.d) and flucytosine (150 mg/kg.d) the mucormycosis healed without the necessity of extensive and disfiguring removal of necrotic tissue . But the blindness in the left eye, caused by occlusion of the central artery, was irreversible. Gen Pharmacol, 1992 Sep, 23(5), 853 - 9 Repeated treatment with quinolones potentiates the seizures induced by aminophylline in genetically epilepsy-prone rats; De Sarro A et al.; 1 . The effects of a chronic treatment with several quinolone derivatives on on the aminophylline-induced convulsions in the genetically epilepsy-prone rat have been investigated . 2 . Two series of experiments have been performed: in the first one animals received the quinolone twice a day for 5 days, then were given aminophylline (80-140 mg.kg-1, i.p.); in the second series of experiments the rats were treated once a day with the quinolone plus 120 mg.kg-1 of aminophylline for 5 days . The changes induced by both treatment protocols on electrocortical activity and on the occurrance of seizures have been evaluated . 3 . Enoxacin reduced the dose of aminophylline necessary for the induction of seizures in a higher degree with respect to the other quinolone derivatives . The derivatives which showed minor proconvulsant properties were ofloxacin, ciprofloxacin and cinoxacin . The potentiation of seizures induced by quinolones appeared a dose-dependent phenomenon which was more evident when high doses of quinolones were used . 4 . The chronic treatment carried out daily with quinolones and aminophylline suggests that additive neurotoxic effects of both classes of drugs may contribute to the increase of severity of seizure scores . 5 . The possible role of GABA-benzodiazepine, excitatory amino acid, purinergic mechanisms as well as the role of pharmacokynetic factors are discussed. Ann Pharmacother, 1992 Sep, 26(9), 1081 - 4 Hypersensitivity and anaphylactoid reactions to ciprofloxacin; Deamer RL et al.; OBJECTIVE: To report three cases of life-threatening hypersensitivity reactions to the oral administration of ciprofloxacin . CASE SUMMARY: Life-threatening hypersensitivity reactions to oral ciprofloxacin, characterized by diffuse, erythematous, nonpruritic, blanching rash, with fever and hypotension, occurred in two HIV-infected patients . One of these reactions was considered anaphylactoid . A similar hypersensitivity reaction was documented in a non-HIV-infected patient . DISCUSSION: Premarketing clinical trials described no reports of life-threatening anaphylactoid hypersensitivity reactions to ciprofloxacin . However, postmarketing surveillance studies have documented their occurrence . Seven cases of anaphylactoid reaction to ciprofloxacin have now been documented in HIV-infected patients . CONCLUSIONS: As with trimethoprim/sulfamethoxazole, HIV-infected people treated with ciprofloxacin may be at special risk for hypersensitivity reactions. Rev Med Chil, 1992 Sep, 120(9), 1027 - 32 {Cutaneous infection by mycobacterium marinum: case report}; Guarda R et al.; A 45 year old male who manipulated tropical fish ponds developed painless nodular plaques in both hands . Biopsy showed mononuclear infiltrate of the dermis with few granulomata . Repeated cultures revealed M . marinum (diagnosis confirmed at the WHO/PAHO Reference Center in Canada) . Good initial results were obtained with single agent therapy with ciprofloxacin . The patient suspended therapy after 11 month and a relapse was observed . Definite cure was obtained with oral cotrimoxazole and topic kanamycin. Therapie, 1992 Sep-Oct, 47(5), 399 - 402 {Drug-induced aseptic meningitis}; Maignen F et al.; Aseptic meningitis is a very rare drug reaction involving non-steroidal antiinflammatory agents (ibuprofen and sulindac), antibiotics (cotrimoxazole, trimethoprim, ciprofloxacin) and miscellaneous drugs such as carbamazepine, human immune globulin and muromonab CD3 . Meningeal symptoms occur a few hours after drug intake and resolve without sequelae within one or two days after drug withdrawal, mainly in young females with systemic lupus erythematosus or mixed connective tissue disease . Biological findings and radiological investigations are not suggestive of an infectious etiology or rheumatological/neurological disturbances . Diagnosis is simple when recurrent episodes coincide with drug ingestion. Cytokine, 1992 Jul, 4(4), 305 - 12 Production and induction of a novel cytotoxin (factor 2) by a human B-cell line; Ni J et al.; The human B-cell line, Karpas 160, was found to produce Factor 1 and 2 (F1 and F2) . F1 was found to be indistinguishable from tumor necrosis factor beta (TNF-beta), while F2 appears to be a new cytotoxin . We used several stimuli alone or in combination to trigger the 160b cells, a subclone of Karpas 160, to produce higher yield of F2 . The optimal culture times, concentrations of cells and a range of stimuli were studied . We found that 20-25 ng/ml of phorbol myristate acetate (PMA) effectively induced the higher production of F2 . Pretreatment of the cells with sodium butyrate enhanced F2 production . Production of TNF but not F2 was inhibited when the cells were cultured with tunicamycin and PDB . When ciprofloxacin or cycloheximide was added to the medium, F2 production in the presence of PMA was amplified . When 160b cells were cocultured with K562 cells, low levels of F2 induction were observed . We found that most types of human tumor cell lines were highly susceptible to F2, but less sensitive or even resistant to TNF . In contrast, normal human cell lines were not susceptible to F2 . Therefore, it appears that F2 could be a new human cytotoxin. Ann Pharmacother, 1992 Jul-Aug, 26(7-8), 930 - 1 Ciprofloxacin-induced psychosis; Reeves RR; OBJECTIVE: To report a case of ciprofloxacin-induced psychosis and to discuss occurrence rates, risk factors, possible etiologies, preventive measures, and treatment courses for this adverse reaction . DATA SOURCES: Case reports and review articles identified by MEDLINE . DATA EXTRACTION: Data from pertinent published sources were reviewed and abstracted . DATA SYNTHESIS: A 49-year-old man developed symptoms of severe psychosis concomitant with ciprofloxacin (250 mg bid) treatment . Central nervous system effects secondary to ciprofloxacin treatment are uncommon and usually consist only of minor dizziness or mild headache, although rare occurrences of seizures and hallucinations have been reported . The mechanism by which ciprofloxacin causes these adverse effects is not fully understood . It has been suggested that quinolones may produce an epileptogenic effect by inhibiting the binding of gamma-aminobutyric acid to its receptor sites in the brain . There is yet no explanation for the occurrence of hallucinations or psychosis . CONCLUSIONS: Caution should be exercised when using ciprofloxacin in the treatment of patients with personality abnormalities or symptoms of psychosis. Trans R Soc Trop Med Hyg, 1992 Jul-Aug, 86(4), 446 - 7 Short-course treatment of typhoid fever with ciprofloxacin in south India; Meskin S et al.; This study assessed the performance of short-course ciprofloxacin for the treatment of 34 adult patients with culture-positive typhoid fever . Patients received ciprofloxacin, 750 mg orally twice daily for 7 d . Measurement of response was based upon time from initial treatment to fever lysis, to afebrile state, and to symptom resolution . Ciprofloxacin-treated patients defervesced in a mean of 3.21 d (+/- 0.56), with stabilization of temperature in 4.0 +/- 0.73 d . After 90 d follow-up, no relapse or carrier was identified . Side effects during therapy were minimal. Trans R Soc Trop Med Hyg . 1992 Jul-Aug;86(4):373. Ciprofloxacin does not achieve radical cure of Plasmodium falciparum infection in Sierra Leone; Stromberg A et al.; Recently, activity in vivo of norfloxacin has been reported against Plasmodium falciparum and, in vitro, ciprofloxacin has been found to be even more potent than norfloxacin . We therefore treated one patient infected with chloroquine-resistant P . falciparum at relatively low parasite density with ciprofloxacin, 200 mg intravenously twice daily for 3 d . This treatment failed to produce radical cure, although some suppressive effect was probably obtained . The growth of the P . falciparum isolate in vitro was inhibited at 12.5 micrograms/ml, whereas the plasma concentration recorded 1 h after infusion was only 1.2 microgram/ml . It is concluded that, if ciprofloxacin is to be used for treatment of malaria, a higher dose than that normally used for bacterial infections is necessary. Indian J Lepr, 1992 Jul-Sep, 64(3), 331 - 40 Correlation between inhibitory effect of quinolones and mycolic acid metabolism in mycobacteria; Patil MA et al.; Mycolic acids are important components having a significant role in maintaining the rigidity of mycobacterial cell wall . They could also be the barrier for penetration of certain drugs into the bacterial cell . A novel in vitro model system was established for assessing the effect of Ciproflaxacin on mycolic acid metabolism in pathogenic mycobacteria M . Kansasii (which has similar mycolic acid pattern to that from M . leprae) and the effect of norfloxacin in M . intracellulare . These test mycobacteria were exposed in their midlogarithmic phase of growth to 0.5, 1, 2, 3, 4, 5 and 6 micrograms ml of ciprofloxacin and norfloxacin respectively for 1, 2 and 24 hours . Ciprofloxacin completely inhibited the synthesis of mycolates in M . kansasii at 3, 4 and 5 micrograms/ml; whereas norfloxacin exhibited its maximum inhibitory action on mycolic acids in M . intracellulare at 6 micrograms/ml for all the durations of exposure . Inhibition of mycolates directly correlated with bacterial viability which was estimated by colony forming units . The effect of quinolones on mycolic acid metabolism appears to be direct and not secondary to DNA gyrase . The results obtained from this study and our previous findings show that mycolic acid metabolism is affected by various groups of drugs, whose primary sites of activity may be different . The findings of the present study may have significant therapeutic implications in leprosy and other mycobacterial diseases. Food Addit Contam, 1992 Jul-Aug, 9(4), 345 - 50 Analysis of enrofloxacin and its metabolite ciprofloxacin in bovine and porcine muscle by high-performance liquid chromatography following cation exchange clean-up; Tarbin JA et al.; A simple and rapid method of analysis for the trace residue determination of enrofloxacin and its metabolite ciprofloxacin has been developed . Clean-up of the samples is by cation exchange solid phase extraction (SPE) and determination made by high-performance liquid chromatography using a base-deactivated column and fluorescence detection . The method has been validated for the determination of residues in bovine and porcine muscle tissue and bacon . Recoveries at the 0.010 mg kg-1 level for enrofloaxacin and ciprofloxacin respectively were 90%, 75% in bovine muscle, 75%, 54% in porcine muscle and 81%, 63% in bacon . Determination to the 0.001 mg kg-1 level in bovine muscle and to the 0.002 mg kg-1 level in porcine muscle and bacon was also carried out . The method has been used as a quantitative screening procedure. J Fam Pract, 1992 May, 34(5), 585 - 91 Risk factors for mortality from lower respiratory infections in nursing home patients; Mehr DR et al.; BACKGROUND . Little is known about the factors that predict whether nursing home residents with lower respiratory infection (LRI) will do well or poorly, although this information is critically important when making treatment decisions . METHODS . Using nursing home and hospital medical records, we performed a case-control study to identify risk factors for death from LRI among residents of a 110-bed, midwestern community nursing home . Three experienced geriatricians aided in the development of an operational definition of an LRI . In a 3 1/2-year period, we identified 26 cases in which the patients died from LRI and 66 control episodes in which the patients recovered from LRI . RESULTS . Compared with those who survived, those who died were 14 times more likely to be totally dependent with respect to activities of daily living (ADL) than the group of patients least ALD-dependent (odds ratio {OR} = 14; 95% confidence interval {95% CI} = 2.85 to 68.87) . After adjusting for ADL, mortality was significantly decreased when a broad-spectrum oral antibiotic (trimethoprim-sulfamethoxazole, cefaclor, amoxicillin-clavulanate, or ciprofloxacin) was used as the initial therapy (OR = .14; 95% CI = .02 to .81) . CONCLUSIONS . Better functional status and initial therapy with broad-spectrum oral antibiotics were strong predictors of surviving an LRI in this population of nursing home patients . The antibiotic effect may be a treatment effect or the consequence of underlying factors leading physicians to select particular antibiotics; however, it appears possible to identify low-risk persons who do not require the aggressive treatment and hospitalization that is often recommended for these patients . An approach to the treatment of nursing home LRI is suggested. Jpn J Antibiot, 1992 May, 45(5), 507 - 11 {Pharmacokinetics and clinical efficacy of ciprofloxacin in aged patients with chronic respiratory diseases}; Teramoto S et al.; Pharmacokinetics and clinical efficacy of ciprofloxacin (CPFX) were investigated in aged patients with chronic respiratory diseases . Serum and sputum concentrations of CPFX were determined upon oral administration of 200 mg CPFX in 6 aged patients with chronic respiratory diseases (mean age = 78.8 +/- 3.2 years, 2 cases diagnosed chronic obstructive pulmonary disease with pneumonia, 3 cases were diagnosed bronchiectasis with acute exacerbation, and 1 case diagnosed chronic lung abscess) . Maximal serum concentrations in these patients were 0.88-1.29 micrograms/ml (mean = 1.08 micrograms/ml) . Thus, maximal serum concentrations of CPFX after oral administration in these aged patients were slightly lower than those in young subjects . However, peak sputum levels of CPFX following oral administration of 200 mg CPFX ranged from 0.53 to 1.47 micrograms/ml at 1-4 hours . These sputum concentrations of the 6 patients were sufficiently high for the inhibition of most infecting organisms in vitro . Clinical responses to CPFX in these 6 patients were good in 5, fair in 1, with an efficacy rate of 100% . Upon administration of CPFX, these 6 patients did not show any adverse reactions . These results suggest that oral administration of CPFX may keep effective levels in serum and sputum over 3 hours in aged patients with chronic respiratory diseases, and good clinical responses should be obtained without side effects in such patients. Antimicrob Agents Chemother, 1992 May, 36(5), 973 - 6 Therapy of experimental murine brucellosis with streptomycin, co-trimoxazole, ciprofloxacin, ofloxacin, pefloxacin, doxycycline, and rifampin; Shasha B et al.; Mice infected with Brucella melitensis were treated with streptomycin, co-trimoxazole, ciprofloxacin, doxycycline, and rifampin intraperitoneally and with ciprofloxacin, ofloxacin, pefloxacin, doxycycline, and rifampin orally for 14 to 21 days . Doxycycline- and rifampin-treated animals (either route) demonstrated a cure rate significantly better than that of controls . Longer therapy periods were associated with a significantly better outcome . Therapy failure was observed in all mice treated with ciprofloxacin, ofloxacin, and pefloxacin administered orally as well as in mice treated intraperitoneally with ciprofloxacin . Our findings demonstrate that treatment of experimental brucellosis in mice with doxycycline and rifampin yields therapeutic results that are superior to those yielded by treatment with quinolones. Eur J Clin Microbiol Infect Dis, 1992 May, 11(5), 447 - 8 Treatment of tularemia with ciprofloxacin; Scheel O et al.; A case of tularemia which occurred after close contact with a cat is presented . After unsuccessful amoxicillin treatment, a two-week course of doxycycline was given whereupon the patient responded well . However, the patient relapsed shortly after and was then given ciprofloxacin for two weeks . The patient then recovered completely . Clinical trials are needed in order to establish whether a quinolone could be the drug of choice for treatment of tularemia. Antibiot Khimioter, 1992 May, 37(5), 42 - 4 {Ofloxacin and ciprofloxacin in the treatment of sexually-transmitted diseases}; Bednova VN et al.; A complex clinico-laboratory++ examination and treatment were made of 76 women with inflammatory processes in the urogenital tract . Gonorrhea, trichomoniasis, chlamydiosis and Ureaplasma infection were detected in 60, 31.4, 41 and 14 per cent of the cases, respectively . There were affections of the rectum by gonococci, chlamydia, ureaplasmas and Trichomonas in 55, 32, 10.6 and 6.6 per cent of the cases, respectively . The frequency of chlamydia in the oropharynx amounted to 30 per cent whereas gonococci and ureaplasma were less frequent i.e . 9 and 1.2 per cent, respectively . The combination of the above pathogens in the rectum were the following: gonococci and chlamydia (15 per cent of the cases), gonococci, chlamydia and Trichomonas (7.3 per cent), gonococci and ureaplasma (7.3 per cent), ureaplasma and chlamydia (7.8 per cent) . In the throat the association of gonococci and chlamydia was detected in 3.7 per cent of the cases . It should be indicated that the signs of sex-transmitted diseases were few, which required careful clinico-laboratory examination of the extragenital foci in the patients with inflammatory urogenital diseases . Ofloxacin showed a high efficacy in the treatment of patients with gonorrhea and ureaplasmosis . Its use in treatment of chlamydiosis proved inexpedient while ciprofloxacin was effective in the treatment of the infection. Am J Med, 1992 Apr 6, 92(4A), 22S - 25S The effects of quinolones on xanthine pharmacokinetics; Robson RA; Caffeine, theobromine, and theophylline are among the most widely consumed compounds in beverages and in pharmaceutical preparations . These methylxanthine alkaloids are metabolized by similar pathways involving demethylation and hydroxylation that are predominantly cytochrome P-450 mediated . In vivo and in vitro evidence suggests that the cytochrome P-450 isozymes involved in the demethylation pathways are distinct from the cytochrome P-450 isozymes involved in the hydroxylation pathways . Although distinctions can be made between demethylation and hydroxylation pathways, the evidence suggests that these different cytochrome P-450 isozymes are under common regulatory control . Any drug inhibiting the family of cytochrome P-450 isozymes involved in the metabolism of the methylxanthines would, therefore, be expected to have a similar effect on theophylline, theobromine, and caffeine . A number of quinolones, including enoxacin, pipemidic acid, ciprofloxacin, norfloxacin, and pefloxacin, have been shown to reduce the clearance of theophylline, while lomefloxacin has no effect on theophylline or caffeine clearance . It has been hypothesized that only fluoroquinolones that form a 4-oxo-metabolite inhibit theophylline clearance . Lomefloxacin, which does not form a 4-oxo-metabolite, would therefore not be expected to inhibit the clearance of theophylline or caffeine . In contrast, ciprofloxacin, which does form a 4-oxo-metabolite, has been shown to reduce theophylline and caffeine clearances by about one third . Another hypothesis for the differences among quinolones suggests that quinolones that have a greater impact on theophylline clearances are more stereochemically similar to theophylline . Substitutions at position 8 on the quinolone nucleus (as in lomefloxacin) would result in stearic hindrance and decrease the structural similarity to theophylline. Am J Med, 1992 Apr 6, 92(4A), 48S - 51S Comparative penetration of lomefloxacin and other quinolones into human phagocytes; Perea EJ et al.; The penetration of lomefloxacin into human polymorphonuclear leukocytes (PMNs) and peritoneal macrophages (PMphis) was evaluated using a fluorometric assay . Lomefloxacin reached high intracellular concentrations into PMNs at extracellular concentrations of 2 and 5 mg/L (cellular to extracellular concentration ratio {C/E} greater than 4) . At the same conditions (20 minutes incubation; extracellular concentrations: 2 mg/L) lomefloxacin uptake by human PMNs (C/E: 7.9 +/- 2.6) was slightly higher than those of norfloxacin (C/E 5.1 +/- 1.8), ciprofloxacin (C/E: 6.2 +/- 2.0), and ofloxacin (C/E 7.1 +/- 2.6) . Lomefloxacin penetration into human PMphis was significantly lower than PMNs but still with C/E ratios greater than 4 . Entry of lomefloxacin into phagocytes was not affected by cell viability but was environmental-temperature dependent . It is concluded that lomefloxacin and the other quinolones evaluated reach high intracellular concentrations in human phagocytic cells. Am J Med, 1992 Apr 6, 92(4A), 18S - 21S Influence of renal function on the pharmacokinetics of lomefloxacin compared with other fluoroquinolones; Blum RA; Fluoroquinolones have similar chemical structures but wide differences in their pharmacokinetic profiles . Disparity in fluoroquinolone elimination is most evident in patients with various degrees of renal insufficiency . Ofloxacin is almost exclusively eliminated by the kidney, whereas pefloxacin is predominantly cleared by the liver . The fluoroquinolones eliminated by both renal and nonrenal routes (hepatic and transintestinal) include norfloxacin, ciprofloxacin, enoxacin, fleroxacin, temafloxacin, and lomefloxacin . The primary renal mechanism of elimination for norfloxacin, ciprofloxacin, enoxacin, fleroxacin, temafloxacin, and lomefloxacin is glomerular filtration and tubular secretion . Both total clearance and renal clearance significantly correlate with creatinine clearance for these fluoroquinolones, and creatinine clearance is a useful clinical marker on which to base dosage adjustments . For some fluoroquinolones, dosage adjustments are recommended when creatinine clearances fall below 30-40 mL/min . This is especially evident for lomefloxacin, temafloxacin, norfloxacin, ciprofloxacin, enoxacin, and fleroxacin . There is very little removal of fluoroquinolones from the plasma during hemodialysis due to their extensive tissue distribution. J Clin Pharm Ther, 1992 Apr, 17(2), 117 - 20 High-performance liquid chromatographic determination of ciprofloxacin in plasma; Mehta AC et al.; This paper describes an accurate, specific and sensitive high-performance liquid chromatographic (HPLC) method for the determination of ciprofloxacin in small samples (0.5 ml) . The samples, after pretreatment by solvent extraction, were eluted on a reversed-phase column and detected by an ultraviolet detector . The results obtained on patient samples are presented. J Clin Pharm Ther, 1992 Apr, 17(2), 111 - 5 A simple high-performance liquid chromatographic assay for ciprofloxacin in human serum; Jim LK et al.; A simple and selective high-performance liquid chromatographic (HPLC) method for the determination of ciprofloxacin in serum has been developed and evaluated . Serum protein was precipitated with acetonitrile . The drug and the internal standard (quinine) were evaluated from a 10 microns U-Bondapack C-18 cartridge at ambient temperature with a mobile phase consisting of acetonitrile: 0.1 M sodium dihydrogen phosphate (20:80%, v/v) adjusted to pH 3.9 with phosphoric acid, and at a flow rate of 2.5 ml/min . The effluent was monitored on a fluorescence detector using an excitation and emission wavelength of 280 and 455 nm, respectively . Each analysis required no longer than 6 min . Quantification was achieved by the measurement of the peak-height ratio and the limit of quantification for ciprofloxacin in serum is 25 ng/ml . The intraday coefficient of variation (CV) ranged from 0.4 to 5.8%, and interday CV from 4.6 to 8.8% at three different concentrations . Relative recovery ranged from 98 to 100.2% at three different concentrations . Preliminary stability tests show that ciprofloxacin is stable for at least 3 weeks in serum after freezing. Ann Pharmacother, 1992 Apr, 26(4), 494 - 5 In vitro delivery of crushed ciprofloxacin through a feeding tube; Druckenbrod RW et al.; OBJECTIVE: The purpose of this study was to determine the relative delivery of ciprofloxacin through a small-bore feeding tube (8 fr, 106 cm, Argyle) . DESIGN: Ciprofloxacin 750-mg tablets were individually ground in a mortar and dissolved in 50 mL of water . Each resulting solution was drawn into a syringe and injected into a glass beaker (n = 10) or through a feeding tube into a beaker (n = 10) over one minute . Syringe apparati were flushed with two 60-mL portions of water . Aliquots from each of the 20 beakers were taken in triplicate, diluted 1:1000 with water, and assayed by HPLC . RESULTS: Ciprofloxacin concentrations (mean +/- SD) for the samples without and with feeding tubes were 11.77 +/- 0.78 mumol/L and 12.16 +/- 0.65 mumol/L, respectively . The 3.3 percent difference is statistically significant (p = 0.04), but clearly is not clinically significant . CONCLUSIONS: Administration of crushed ciprofloxacin through a small-bore feeding tube in the manner described does not result in any measurable loss of drug delivered to the gastrointestinal tract. Arch Intern Med, 1992 Mar, 152(3), 617 - 21 An evaluation of the quinolone-theophylline interaction using the Food and Drug Administration spontaneous reporting system; Grasela TH Jr et al.; A review of the Food and Drug Administration's spontaneous reporting system identified 48 reports of adverse events in patients who received concomitant therapy with ciprofloxacin (n = 39) or norfloxacin (n = 9) and theophylline . The mean (SD) age of these cases was 68.4 (18.5) years; 25 patients (52%) were female . The mean percent change in theophylline concentrations was 114%, with a range of 32% to 308% following the addition of a quinolone to the patient's theophylline regimen . Fourteen (36%) of the 39 patients receiving ciprofloxacin and three (33%) of the nine patients receiving norfloxacin experienced a seizure . The accumulated evidence suggests that extreme caution should be used when quinolones are prescribed in conjunction with theophylline, particularly in elderly patients . Further research is required to identify risk factors that will more specifically predict the magnitude of the interaction. J Assoc Physicians India, 1992 Mar, 40(3), 176 - 8 Chloramphenicol and ciprofloxacin in enteric fever--cost-effectiveness; Narendranathan M et al.; Clinical decision analysis is a technique which is used to deal with uncertainities in clinical medicine . We used this technique to compare the cost-effectiveness of chloramphenicol and ciprofloxacin in the treatment of enteric fever . The study shows that the most economical alternative can be predicted if the cost of hospital stay and the sensitivity of the organism to chloramphenicol are known . Thus if the hospital costs are Rs 50/- per day, chloramphenicol will be the drug of choice if more than 52% of the organisms are sensitive to the drug . At lower levels of sensitivity to chloramphenicol, ciprofloxacin will be the drug of choice. Geburtshilfe Frauenheilkd, 1992 Mar, 52(3), 165 - 70 {Treatment of acute salpingitis with tetracycline/metronidazole with or without additional balneotherapy, Augmentin or ciprofloxacin/metronidazole: a second-look laparoscopy study}; Gerber B et al.; 110 patients suffering from laparoscopical verified salpingitis and desire for a baby, were treated with tetracycline (oxytetracycline or doxycycline; TC)/metronidazole (n = 67), augmentan (n = 22) or cipropfloxacin/metronidazole (n = 21) . After an average period of 11.6 weeks, all patients underwent second-look laparoscopy with dye insufflation . In 34 patients treated with TC/metronidazole, the effects of additional physio-therapeutical measures were examined under conditions as they prevail in a Spa . 33 patients without balneotherapy served as controls . All the 4 groups were comparable (p greater than 0.05) in respect of mean age, percentage, share of nulliparous women, salpingitis gonorrhoica, contraceptive behaviour and also of the stage of salpingitis . All antibiotic regimens used resulted in a prompt decrease of inflammatory clinical signs after five days (temperature, blood sedimentation rate, leukocytes) . Only 2 of 34 patients treated by additional cure at a Spa reported complaints, whereas complaints were reported by 14 of 33 control patients (p less than 0.01), 7 of 22 (p less than 0.01) treated with augmentan and to 7 of 21 (p less than 0.01) treated with ciprofloxacin/metronidazole . The tubal occlusion rates amounted to 33.3% (TC/metronidazole), 32.3% (TC/metronidazole and balneotherapy), 22.7% (augmentan) and 23.8% ciprofloxacin/metronidazole . The differences did not attain statistical significance (p greater than 0.05) . With regard to adhesions, there were, likewise, no significant differences between findings at first laparoscopy and second look-laparoscopy, respectively . It is concluded, that additional physiotherapeutic measures, after antibiotic therapy of acute salpingitis, reduce the frequency of lower abdominal pain, but do not result in an improvement of tubal occlusion and reduction of adhesions.(ABSTRACT TRUNCATED AT 250 WORDS) Antimicrob Agents Chemother, 1992 Mar, 36(3), 682 - 3 In vitro activities of five quinolones against Chlamydia pneumoniae; Hammerschlag MR et al.; The in vitro susceptibilities of 10 strains of Chlamydia pneumoniae were determined for five quinolones, including ciprofloxacin, ofloxacin, fleroxacin, temafloxacin, and sparfloxacin . Sparfloxacin was the most active compound tested, followed by ofloxacin and temafloxacin . Ciprofloxacin and fleroxacin were the least active . The use of HEp-2 cells for testing C . pneumoniae resulted in larger inclusions but essentially the same endpoints as were seen with use of HeLa 229 cells. J Rheumatol, 1992 Feb, 19(2), 216 - 22 Protective effects of ciprofloxacin against type II collagen induced arthritis in rats; Breban M et al.; Ciprofloxacin, a new fluoroquinolone antibiotic, inhibits the in vitro production of interleukin 1 beta and tumor necrosis factor alpha by monocytes . We investigated its activity against type II collagen induced arthritis in rats . It exerted a dose dependent preventive effect at 50 and 75 mg/kg/day against clinical and histologic features of collagen induced arthritis without any influence on the production of anticollagen antibodies and alpha 1-acid glycoprotein . This effect was reversible after early removal of the treatment . Ciprofloxacin did not inhibit collagen induced arthritis in adrenalectomized rats but rather caused an exacerbation of the disease . Its effect was not modified by the simultaneous administration of an antiglucocorticoid, RU 40555. Int J Clin Pharmacol Ther Toxicol, 1992 Feb, 30(2), 66 - 8 Comparative bioavailability of two brands of ciprofloxacin: an Indian study; Suthakaran C et al.; A randomized crossover study was carried out to determine the bioavailability of two commercially available brands of ciprofloxacin after oral administration in healthy volunteers . There were no significant differences in the pharmacokinetic parameters that characterize bioavailability between the two brands . It is therefore concluded that there is no bioinequivalence between these ciprofloxacin brands. Chemotherapy, 1992, 38(4), 271 - 4 Ciprofloxacin plus vancomycin versus ceftazidime plus gentamicin in the treatment of pneumonia in granulocytopenic patients with or without venous catheters . Short communication; Krcmery V Jr et al.; 58 granulocytopenic patients with confirmed bronchopneumonia were divided retrospectively into two groups for this pilot study: group 1 included neutropenic patients with venous catheters who were treated with ciprofloxacin (CIP; 200-300 mg, i.v . b.i.d.) + vancomycin (VAN; 0.5-1 g, i.v . b.i.d.), and group 2, which included patients without venous catheters treated with ceftazidime (2 g, i.v . t.i.d.) + gentamicin (1 mg/kg, i.v . t.i.d.) . Pneumonia was diagnosed clinically and radiologically in all patients; 92.3% in group 1 and 46.8% in group 2 were also microbially confirmed . Mixed infections were present in most patients . 3 of 26 patients (11.5%) in group 1 and 9 of 32 (20.1%) in group 2 did not recover while 88.5% in group 1 and 71.9% in group 2 recovered . CIP + VAN seems to be more effective in treating pneumonia in neutropenic patients, with only 1 patient in the group suffering an adverse effect compared with 5 in group 2. Mutagenesis, 1992 Jan, 7(1), 47 - 9 Induction of ribonucleoside diphosphate reductase gene transcription by chemicals in Escherichia coli; Sitjes J et al.; A fusion between the promoter of the nrdA gene of Escherichia coli and the lacZ gene has been constructed, and the induction of nrdA gene expression by 20 organic and 20 inorganic chemicals has been studied . The inducing compounds of the SOS genes, such as bleomycin, captan, ciprofloxacin, enoxacin, hydroxyurea, N-methyl-N'-nitro-N-nitrosoguanidine, mitomycin C, nalidixic acid, ofloxacin and hexavalent chromium compounds also trigger the expression of the nrdA gene . Other chemicals such as aluminium, manganese and zinc salts, reported as negative in the SOS Chromotest, are also inducers of the nrdA gene . These results suggest that ribonucleoside diphosphate reductase transcription is increased by chemicals able to either block DNA synthesis or to alter the enzymes participating in the DNA replication . Induction of nrdA gene is an effect to be further considered in the study of alterations produced by physical or chemical treatments which act upon DNA metabolism. Ann Pharmacother, 1992 Jan, 26(1), 11 - 3 Effect of the addition of ciprofloxacin on theophylline pharmacokinetics in subjects inhibited by cimetidine; Davis RL et al.; OBJECTIVE: Although the effect of individual enzyme inhibitors on hepatic microsomal enzyme activity has been studied extensively, little data exist on the effects of combinations of inhibiting agents . The purpose of this study was to investigate the effect of the addition of a second hepatic oxidative enzyme inhibitor on the inhibition of metabolism in subjects already maximally inhibited by cimetidine . Ciprofloxacin was used as the second inhibitor . DESIGN: In a randomized crossover sequence, subjects received theophylline 5 mg/kg on day 6 of therapy with cimetidine 2400 mg/d, ciprofloxacin 1 g/d, both drugs, or while drug-free . SETTING: National Institutes of Health-funded General Clinical Research Center . PARTICIPANTS: Eight normal volunteers (6 men, 2 women; mean age 25.2 y) . OUTCOME MEASURES: Theophylline pharmacokinetic parameters after each treatment were determined by model independent pharmacokinetic analysis . Statistical analysis of the data for differences between treatments was assessed by ANOVA for repeated measures . RESEARCH: When administered alone, ciprofloxacin and cimetidine caused a significant increase in theophylline elimination half-life and a decrease in clearance . Theophylline elimination half-life was significantly longer during combined therapy compared with either drug alone . Theophylline clearance was lower during combined treatment, although this relationship did not reach statistical significance . CONCLUSIONS: The addition of a second enzyme inhibitor in subjects receiving maximally inhibiting doses of cimetidine can produce a further decrease in the hepatic metabolism of drugs that are metabolized by the cytochrome P-450 microsomal enzyme system . As cimetidine and ciprofloxacin are frequently used together for a variety of common clinical indications, clinicians should be aware of this drug interaction and should consider that a similar effect may occur when other enzyme inhibitors are used concomitantly. Antimicrob Agents Chemother, 1992 Jan, 36(1), 150 - 2 Efficacy of ciprofloxacin for treatment of Brucella melitensis infections; al-Sibai MB et al.; The effectiveness of treatment of human brucellosis caused by Brucella melitensis with ciprofloxacin alone was investigated in a prospective nonrandomized study . Subjects with central nervous system involvement, endocarditis, or severe renal dysfunction; children under 16 years of age; and pregnant women were excluded from the study . Of 19 patients, 16 completed the study; 7 were diagnosed as having acute systemic brucellosis, and 9 had acute brucella arthritis-diskitis . A rapid response to ciprofloxacin was seen in all 16 patients, but the blood cultures of 1 patient remained positive and the treatment was changed . During a 104-week follow-up period, 4 of the 15 responding patients relapsed or were reinfected within 8 to 32 weeks after completion of therapy . We conclude that treatment with ciprofloxacin alone, although effective for the acute symptoms, is associated with an appreciable rate of relapse; therefore, it should be given with other agents for treatment of brucellosis. Clin Infect Dis, 1992 Jan, 14(1), 272 - 84 Interactions of fluoroquinolones with other drugs: mechanisms, variability, clinical significance, and management; Radandt JM et al.; Several important interactions of fluoroquinolones with other drugs have been reported in the literature . The absorption of all fluoroquinolones is almost entirely inhibited by concomitant administration of di- and trivalent cations, such as aluminum and magnesium contained in antacids . The inhibition of absorption can be significant and can potentially lead to the failure of treatment, even when fluoroquinolone doses are separated from antacid doses by hours . Certain isozymes of the cytochrome P-450 system are selectively inhibited by some fluoroquinolones . The metabolism of theophylline and caffeine is inhibited by enoxacin and ciprofloxacin such that the dosage of theophylline may need to be reduced in order to avoid toxicity . In contrast, ofloxacin and norfloxacin cause less inhibition of the metabolism of these compounds, and reduction of the theophylline dosage is not routinely required . Evidence regarding the effect of fluoroquinolones on the disposition of other drugs known to be metabolized, such as warfarin and cyclosporine, is inconclusive . In summary, the safe and effective use of fluoroquinolone antibiotics requires careful consideration of concomitant drug therapy. Clin Infect Dis, 1992 Jan, 14(1), 156 - 61 Successful treatment of pulmonary infection due to Mycobacterium chelonae: case report and review; Singh N et al.; During the past decade, Mycobacterium chelonae has been recognized with increasing frequency as a pulmonary pathogen . A review of previously reported cases reveals that most patients with pulmonary infections due to M . chelonae are nonimmunosuppressed but have underlying chronic lung disease . The infection is notably absent among blacks . M . chelonae organisms are characterized by a high degree of in vitro resistance to antituberculous drugs, and attempts at eradicating the organism through chemotherapy have been largely unsuccessful . The case of a 63-year-old previously healthy woman with progressive bilateral pulmonary disease due to M . chelonae is reported; she was treated successfully with a combination of cefoxitin and orally administered ciprofloxacin . Our experience supports the use of quinolones in combination with other active agents for the treatment of pulmonary infection due to M . chelonae. J Pak Med Assoc, 1992 Jan, 42(1), 9 - 10 Role of ciprofloxacin in typhoid fever; Akhtar MA et al.; A study was conducted to investigate the effects of ciprofloxacin in typhoid fever and to compare its efficacy with chloramphenicol . Eighty patients between 20-45 years with positive blood culture were included in the study . Seventy five percent patients treated with ciprofloxacin became afebrile within 72 hours while with chloramphenicol it took upto 120-144 hours for the same percentage of patients to become afebrile . Four patients resistant to chloramphenicol, cotrimoxazole and ampicillin/amoxycillin, also responded to ciprofloxacin . There were no significant adverse effects indicating that ciprofloxacin is safe and effective drug for resistant and nonresistant cases of typhoid fever. Am J Nephrol, 1992, 12(4), 271 - 3 Ciprofloxacin-induced acute interstitial nephritis; Bailey JR et al.; Acute renal failure is a complication attributed to numerous medications . Few cases linked to the newer fluoroquinolones have been described . We report a case of acute interstitial nephritis confirmed by renal biopsy that developed in a patient within days of starting ciprofloxacin therapy . A review of the literature reveals common clinical manifestations of this rare adverse effect . Clinicians should be aware of this potential complication of ciprofloxacin use. Intensive Care Med, 1992, 18(7), 437 - 8 Ciprofloxacin levels in a patient undergoing veno-venous haemodiafiltration; Barrie JR et al.; Haemofiltration is a popular technique for removal of fluid and small to medium size molecules in critically ill patients . Whilst there is often good information on drug disposition in chronic renal failure, there is a lack of information available to guide Intensivists on how to prescribe drugs in patients in acute renal failure undergoing haemofiltration or haemodiafiltration. Adv Perit Dial, 1992, 8, 227 - 9 Relationship between peritonitis and exit site infections in CAPD; Eisele G et al.; This study was designed to retrospectively review the experience in this center with oral ciprofloxacin 500 mg bid and ip vancomycin 25 mg/L in the treatment of CAPD-related exit site infections and to determine the relationship between exit site infections and peritonitis . There were 48 patients with 172 episodes of infection (23 had both infections, 22 had peritonitis only, 3 had exit site infections only) . Thus, exit site infections occur infrequently in the absence of peritonitis (23% of occasions) . Of the 35 patients who had peritonitis as the first infection, 13 (37%) subsequently developed an exit site infection . The mean +/- SD period from an initial peritonitis to a subsequent exit site infection in these patients was 8.2 +/- 8.0 (range 1-28) months . Of the 22 patients with 34 exit site infections, there were 15 (44%) treatment failures, of which 10 (67%) were relapses or possible relapses . S . aureus was the most common isolate . 5% of exit site infections were culture negative . Follow-up was incomplete for many patients resulting in many instances of no further cultures, and compliance could not be assured . This combination was associated with a high incidence of treatment failures in this setting. Pharmacotherapy, 1992, 12(5), 369 - 75 Comparative assessment of the effect of lomefloxacin, ciprofloxacin, and placebo on cerebral blood flow, and glucose and oxygen metabolism in healthy subjects by positron emission tomography; Bednarczyk EM et al.; The mechanism by which the fluorinated quinolones produce central nervous system (CNS) effects is currently unknown . We measured the effect of lomefloxacin on cerebral blood flow and metabolism using positron emission tomography . Eighteen healthy, nonsmoking volunteers were randomized to receive lomefloxacin 400 mg, ciprofloxacin 750 mg, or placebo given in a single-blind fashion every 12 hours for 72 hours, the time window for maximum lomefloxacin CNS effects . Subjects receiving lomefloxacin had a mean (+/- SEM) cerebral blood flow (CBF) of 46 (2.9) ml/min/100 g, glucose metabolism (FDG) 4.7 (0.4) mg/min/100 g, oxygen metabolism (OM) 3.3 (0.3) ml/min/100 g, and oxygen extraction (%OM) 0.4 (0.04) . Posttreatment values were 43 (3.6) ml/min/100 g, 4.2 (0.4) mg/min/100 g, 2.6 (0.3) ml/min/100 g, and 0.4 (0.03), respectively . Values for subjects receiving ciprofloxacin were CBF 44.8 (1.6) ml/min/100 g, FDG 4.9 (0.7) mg/min/100 g, OM 4.1 (0.4) ml/min/100 g, and %OM 0.6 (0.03) at baseline, and 40.3 (3.5), 4.5 (0.6), 3.4 (0.4), and 0.5 (0.09), respectively, after treatment . For placebo-treated subjects, baseline values were CBF 41.4 (1.9) ml/min/100 g, FDG 4.9 (0.5) mg/min/100 g, OM 3.3 (0.4) ml/min/100 g, and %OM 0.5 (0.07), and respective posttreatment values were 42.1 (2.3), 5.0 (0.6), 3.5 (0.3), and 0.5 (0.02) . No effect was observed on visual (qualitative), blinded reading of the scans . No significant effect on cerebral blood flow or metabolism was detected . We conclude that short-term administration of lomefloxacin or ciprofloxacin to healthy volunteers does not have a significant effect on cerebral blood flow, or on oxygen or glucose metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) Nephrol Dial Transplant, 1992, 7(8), 848 - 54 Pharmacokinetics of ciprofloxacin and vancomycin in patients with acute renal failure treated by continuous haemodialysis; Davies SP et al.; To determine appropriate doses of ciprofloxacin and vancomycin for septic patients with acute renal failure (ARF) treated by continuous arteriovenous and venovenous haemodialysis, (CAVHD/CVVHD), we performed pharmacokinetic studies in patients receiving these antibiotics . All patients were treated by CAVHD/CVVHD using Hospal AN69S 0.43 m2 filters and Fresenius 1.5% peritoneal dialysis fluid at dialysate flow rates (Qd) of 1 and 2 l/h . Patients received ciprofloxacin 200 mg i.v . 12-hourly (n = 6) or 8-hourly (n = 5); vancomycin 1 g i.v . was administered to 10 patients approximately every 48 h to maintain therapeutic plasma levels . For ciprofloxacin, volume of distribution (Vdarea) was 136.5 +/- 9.81, terminal elimination half-life (t1/2) 6.4 +/- 0.8 h, and total body clearance (TBC) 264.3 +/- 22.9 ml/min (mean +/- SEM) . Mean sieving coefficient (S/C) was 0.76 +/- 0.05 and filter clearances at Qd 1 and 2 l/h were 16.2 +/- 1.9 and 19.9 +/- 1.1 ml/min respectively . For vancomycin, Vdarea was 60.7 +/- 5.11, t1/2 24.7 +/- 2.6 h and TBC 31.0 +/- 4.6 ml/min . Mean S/C was 0.66 +/- 0.08 and filter clearances at Qd 1 and 2 l/h 12.1 +/- 2.0 and 16.6 +/- 2.0 ml/min . These data suggest that patients with ARF treated by CAVHD/CVVHD should be given ciprofloxacin 200 mg i.v . 8-12-hourly and vancomycin every 48 h. Nippon Yakurigaku Zasshi, 1992 Jan, 99(1), 45 - 54 {Effects of the combination of new quinolones and a nonsteroidal anti-inflammatory drug, fenbufen, on the EEG of rabbits}; Suzuki T et al.; A combination of fenbufen, a non-steroidal anti-inflammatory drug and the new quinolone produces a central stimulating action . To confirm the action, we used 6 kinds of new quinolones: enoxacin, norfloxacin, ofloxacin, ciprofloxacin, lomefloxacin and tosufloxacin in this experiment . The convulsive effects of these drugs were tested on the EEG recorded from the neocortex and subcortical regions of the rabbits . Animals treated with fenbufen (50-200 mg/kg, p.o.) tended to have a high amplitude slow wave in their EEG . Rabbits treated with the new quinolones at the dose of 100 mg/kg, p.o., with the exception of tosufloxacin, also tended to show a high amplitude slow wave in their EEG . Each new quinolone given 30 min after fenbufen (50 mg/kg, p.o.) elicited characteristic spikes on the EEG . Then, high-frequency-spikes and epileptiform seizure waves appeared for a long experimental period with this combination . The combination of fenbufen and tosufloxacin (100-400 mg/kg, p.o.) caused no changes in EEG and behavior . The spike and epileptiform wave could be suppressed only temporarily with diazepam (1-4 mg/kg, i.v.) . These results suggest that combined use of fenbufen and one of the new quinolones, except for tosufloxacin, produces the seizure . Not only GABA but also several other mechanisms in the central nervous system may be involved in the convulsion. Arch Virol, 1992, 122(3-4), 263 - 9 Lack of in vitro antiviral activity of fluoroquinolones against herpes simplex virus type 2; Pessina A et al.; The antiviral activity against herpes simplex virus type 2 (HSV-2) of five fluoroquinolones (ciprofloxacin, lomefloxacin, ofloxacin, pefloxacin, rufloxacin) was tested in vitro . Their efficacy was evaluated as reduction of the cytopathic effect (CPER) exerted by HSV-2 on Vero cells in comparison with novobiocin and acycloguanosine . Our results show a very poor antiviral effect of five quinolones (CPER50 = 200 mg/l) that was comparable with their cytotoxicity (TCIC50 less than 200 mg/l) . Novobiocin shows a lower toxicity (TCIC50 = 400 mg/l) and a slight antiviral activity (CPER50 = 120 mg/l) . Acycloguanosine shows a TCIC50 greater than 400 mg/l and a CPER50 of 3.125 mg/l . The therapeutic indices gave values ranging from 0.12 to 2 for quinolones, of 3.3 for novobiocin, and greater than 128 for acycloguanosine . The antiviral efficacy of acycloguanosine was not affected by concentrations of quinolones active against bacteria (1-10 mg/l) whereas it was drastically reduced by higher doses of quinolones (greater than 50 mg/l) . Our data suggest that fluoroquinolones cannot be considered drugs able to inhibit HSV-2 replication in vitro. Pneumonol Alergol Pol, 1992, 60(1-2), 36 - 9 {Effect of ofloxacin, ciprofloxacin and nalidixic acid on serum theophylline level in patients treated with methylxanthine preparations}; Chyrek-Borowska S et al.; The effect of two new quinolones, ofloxacin and ciprofloxacin and nalidixic acid on serum theophylline level in 17 asthma patients treated with methylxanthines was evaluated . Each quinolone was administered one tablet twice daily to all patients for three days . Blood samples were taken before quinolone administration and 1 h, 3h and 5 h after taking the drug on the first day . Last sample was taken 5 h after quinolone administration on the third day of therapy . The serum theophylline concentration was determined by 3 M Theo FAST test . It was found that in the patients treated with ciprofloxacin serum theophylline level in all samples was significantly higher as compared with the control sample . In the patients receiving ofloxacin the theophylline level only 1 h after receiving the drug the increase was statistical significant . Nalidixic acid had no influence on serum theophylline concentration . As these studies show, the new quinolones should be applied with great caution in patients treated with high doses of methylxanthines or in patients with decreased methylxanthines clearance . In patients with chronic obturative diseases and pulmonary infections the safer drug would appear to be ofloxacin. Am J Med, 1991 Dec 30, 91(6A), 42S - 44S Assessment of temafloxacin neurotoxicity in rodents; Giardina WJ; Temafloxacin hydrochloride (HCl) was studied in fenbufen-treated mice and for its effects on the locomotor activity of rats . Mice were observed for convulsions for 90 minutes after the administration of temafloxacin HCl (100 mg/kg orally {p.o.}), ciprofloxacin HCl (100 mg/kg p.o.), enoxacin (100 mg/kg p.o.), or oxolinic acid (100 mg/kg p.o.) . The quinolones were coadministered with either saline (0.2 mL p.o.) or fenbufen (100 mg/kg p.o.), a nonsteroidal antiinflammatory compound . No convulsions occurred following the administration of the quinolones with saline . Clonic convulsions occurred in 90% of mice receiving enoxacin and fenbufen and in 20% of mice receiving ciprofloxacin HCl and fenbufen . No convulsions occurred in mice receiving temafloxacin HCl or oxolinic acid with fenbufen . At doses of 30, 100, and 300 mg/kg p.o., temafloxacin HCl and enoxacin had no effect on locomotor activity of rats, but oxolinic acid markedly stimulated locomotor activity . The lack of central nervous system (CNS) stimulation and the absence of interaction with fenbufen suggest that temafloxacin may have less potential for adverse CNS effects than other quinolone compounds. Am J Med, 1991 Dec 30, 91(6A), 38S - 41S Comparison of organ-specific toxicity of temafloxacin in animals and humans; Krasula RW et al.; This article summarizes animal studies conducted to determine the toxic and mutagenic potential of temafloxacin . The four target tissues of potential concern with fluoroquinolone use are the kidney, the eye, the weight-bearing joints of young animals, and the central nervous system . Based on the results of these studies in rats and dogs, it appears unlikely that crystalluria or nephrotoxicity will occur in humans who receive temafloxacin . Pre-marketing clinical trials in humans (n = 5,308) correlate well with chronic toxicity animal studies, reporting no crystalluria or clinically significant nephrotoxicity . Reversible electroretinographic (ERG) changes in dog studies were demonstrated only with the administration of high temafloxacin dosages . A Phase I study evaluating the safety of temafloxacin at 600 mg b.i.d . for 14 days in human subjects reported no significant changes in ophthalmologic parameters . Evidence of cartilaginous joint damage was observed in puppies receiving oral temafloxacin, in young dogs receiving intravenous temafloxacin, and in a single dog receiving a lethal dosage in a dose range-finding study . However, these toxic findings were not evident in any dogs in the subacute or chronic oral toxicity studies or in a longer duration intravenous study . Although limited evidence would suggest that young children may not be at risk, thorough clinical investigations of quinolones in these patients have only recently been initiated . Signs of central nervous system toxicity caused by temafloxacin were absent in two rodent studies, during which clonic convulsions were induced by concomitant use of fenbufen plus enoxacin or ciprofloxacin, and in human subjects evaluated by positron emission tomography . Temafloxacin, contrary to most other quinolones, was considered nonmutagenic in all mutagenicity tests conducted . In reproductive studies, temafloxacin was not uniquely toxic to the developing conceptus in the laboratory rat, mouse, rabbit, or primate . Based on these animal studies, temafloxacin appears to be non-mutagenic and to have a low potential for producing renal or ocular toxicity; however, like other quinolones, it should not be routinely used in children or pregnant women because of evidence of cartilage damage reported in young dogs . Premarketing clinical trials to date confirm the safety of temafloxacin use in adults. Am J Med, 1991 Dec 30, 91(6A), 101S - 105S Efficacy of temafloxacin versus ciprofloxacin or amoxicillin for lower respiratory tract infections in smokers and the elderly; Davey PG; The purpose of this study was to determine the effects of smoking history and age on the efficacy and safety of temafloxacin versus ciprofloxacin or amoxicillin in patients with lower respiratory tract infections (LRTIs) . Data were pooled from six clinical trials designed to evaluate the efficacy and safety of temafloxacin in bacterial infections of the lower respiratory tract . Patients were selected for this analysis based on smoking history (n = 256) and age (greater than or equal to 65 years of age {n = 328}) . Results in the smoker and elderly subgroups were compared between treatment groups and with those in nonsmoker and nonelderly subgroups . Temafloxacin 300 mg or 600 mg b.i.d., ciprofloxacin 500 mg or 750 mg b.i.d., or amoxicillin 500 mg t.i.d . was administered orally for 7-14 days . Patients were assessed at enrollment, on study days 3-7, 24-72 hours post-treatment, and at 5-9 days post-treatment . Temafloxacin and the reference drugs demonstrated comparable clinical efficacy for treatment of LRTI in smokers (93.7% and 92.5%, respectively) and the elderly (94.6% and 89.3%, respectively) . However, eradication of baseline pathogens in individual patients was significantly more common after temafloxacin therapy than that following treatment with the reference drugs in both smokers (99.2% versus 91.2%, p = 0.006) and elderly patients (97.5% versus 91.5%, p = 0.028) . Overall, eradication rates for pretreatment pathogens were also significantly higher in smokers (99.3% versus 91.8%, p = 0.006) and in the elderly (97.8% versus 92.3%, p = 0.027) . Neither age nor smoking status had a consistent effect on the rate of premature discontinuation of study drugs . Adverse events occurred at a similar rate between treatment groups in the elderly and in the smokers . Temafloxacin appears to be a promising alternative to therapy with either ciprofloxacin or amoxicillin in the treatment of respiratory infections in high-risk patients, smokers, and the elderly. Antimicrob Agents Chemother, 1991 Dec, 35(12), 2521 - 5 Steady-state pharmacokinetics of ciprofloxacin in plasma from patients with nosocomial pneumonia: penetration of the bronchial mucosa; Fabre D et al.; A 30-min intravenous (i.v.) infusion of 200 mg of ciprofloxacin was administered twice daily to 12 patients with nosocomial pneumonia scheduled to undergo diagnostic fiberoptic bronchoscopy . The pharmacokinetics of ciprofloxacin were examined at the presumed steady state after 5 days of treatment . Eleven successive plasma samples were collected in the interval from 0 to 12 h after administration, and bronchial mucosa samples were taken 2 h after administration . Concentrations of drug in all samples were assayed by high-performance liquid chromatography with fluorimetric detection . The results showed that the kinetics in plasma did not differ from those determined previously in healthy volunteers . The mean concentrations in plasma peaked at 4.94 +/- 2.90 mg/liter at the end of infusion . The terminal half-life was 4.95 +/- 2.81 h, and the mean residence time 6.13 +/- 3.17 h . A large volume of distribution was calculated: 2.59 +/- 1.43 liters/kg . Mean total body clearance was 23.3 +/- 10.1 liters/h . The concentrations in bronchial mucosa reached 21.6 +/- 5.63 micrograms/g 2 h after drug intake . The tissue-versus-plasma concentration ratios ranged from 10.1 to 26.3 (mean value, 16.9 +/- 5.43) . After 6 to 12 days of i.v . treatment, four patients were switched to oral ciprofloxacin . We propose a model for the simultaneous fit of the concentration-time curves obtained after i.v . infusion and oral dosing . The concentrations in tissue observed in this study were in excess of the MICs for bacteria considered to be susceptible to ciprofloxacin. Am J Otol, 1991 Nov, 12(6), 477 - 9 The fluoroquinolones; Brody T et al.; At the Eastern Section Meeting of the Triological Society January 26, 1990, Levinson et al reported outstanding success with ciprofloxacin in the treatment of malignant otitis externa . Moreover, several of the individuals so managed had been refractory to conventional therapy with semisynthetic penicillin and aminoglycoside protocols . This new class of antibiotics may result in a profound change in our management of patients with otologic, neurotologic, and skull base infections. Antimicrob Agents Chemother, 1991 Nov, 35(11), 2215 - 8 In vitro and in vivo ciprofloxacin pharmacokinetics in human neutrophils; Garraffo R et al.; Early in vitro investigations have shown that ciprofloxacin is concentrated within human neutrophils (polymorphonuclear leukocytes {PMNs}) at between 3 and 11 times the extracellular concentration . The elution of ciprofloxacin from cells is relatively rapid when the extracellular concentration is reduced . In order to estimate the in vivo intracellular penetration of ciprofloxacin and to determine its intracellular pharmacokinetics, PMNs were recovered from blood samples drawn from healthy volunteers at different times during a 24-h period after they were given a 750-mg oral dose . High-performance liquid chromatographic determination of ciprofloxacin in serum and cells showed that the intracellular/serum ratio was 3.7 at 1.5 h (maximum concentration of drug in serum), 5.7 at 12 h, and 20 at 24 h . The area under the curve ratio was 3.73 . The mean elimination half-lives of ciprofloxacin were 3.7 and 6.2 h in serum and PMNs, respectively . These data show that in vivo findings are in agreement with in vitro findings . The large uptake of ciprofloxacin by PMNs combined with a prolonged intracellular half-life described under the conditions of human therapy should provide the basis for the use of ciprofloxacin in infections caused by susceptible intracellular bacteria. DICP, 1991 Nov, 25(11), 1249 - 58 Quinolone-cation interactions: a review; Lomaestro BM et al.; The quinolone class of antibiotics is enjoying a recent resurgence in interest and use due to the development of improved compounds . Norfloxacin, ciprofloxacin, and, most recently, ofloxacin have been marketed . Enoxacin and other agents are in various stages of investigation . These newer compounds are often used for indications not successfully treated by the original quinolones, or in some cases, not optimally treated with any previously available oral antibiotic . A potential problem with the increasing use of quinolone-type antibiotics for systemic illness is the chelation and inactivation of these compounds by several cations . One outcome of these potential interactions is a possible reduction in bioavailability and effectiveness of quinolone compounds . A review of the literature on quinolone-cation interactions, in vivo and in vitro significance, and recommendations to avoid potential problems are provided. Eur J Clin Microbiol Infect Dis, 1991 Nov, 10(11), 969 - 71 Fluorometric and high-performance liquid chromatographic measurement of quinolone uptake by human neutrophils; Pascual A et al.; A fluorometric assay, based on the natural fluorescence of the quinolone nucleus, and high-performance liquid chromatography (HPLC) were compared to determine the penetration of six quinolones (norfloxacin, ciprofloxacin, ofloxacin, fleroxacin, lomefloxacin and temafloxacin) into human polymorphonuclear neutrophils (PMN) . Intracellular concentrations after 20 min incubation of the cells with 10 and 25 mg/l were three or more times higher than the extracellular ones . There were no statistical differences between the two methods . At lower extracellular concentrations (2 and 5 mg/l) the intracellular levels of all the quinolones tested were undetectable by HPLC . Fluorometry is a useful method for determining the intracellular penetration of quinolones . The usefulness of HPLC, however, is questionable since it requires great volumes of cells and extracellular concentrations much higher than the therapeutic ones. Pediatr Infect Dis J, 1991 Oct, 10(10), 723 - 9 Clinical, radiologic and magnetic resonance monitoring for skeletal toxicity in pediatric patients with cystic fibrosis receiving a three-month course of ciprofloxacin; Schaad UB et al.; Because of arthropathic toxicity observed in growing animals the quinolone antibiotics are not recommended for use in children . Recently, magnetic resonance imaging performed in juvenile animals was found to predict ciprofloxacin-induced cartilage damage at the knee joint . We conducted clinical, laboratory, radiologic and magnetic resonance imaging investigations in 13 prepubertal (age range, 6 to 13 years) and 5 postpubertal patients (age range, 14 to 24 years) with cystic fibrosis at the start and the end of a 3-month course of ciprofloxacin (30 mg/kg of body weight/day, administered orally in two equal doses) and at follow-up 4 to 6 months later . Our comprehensive monitoring gave no evidence for arthropathogenicity . Detailed physical skeletal function tests, height velocity values, laboratory studies of bone metabolism and conventional radiographs of both knees revealed no abnormalities . Moreover the serial magnetic resonance images of the left knee demonstrated lack of joint effusion, intact two-layer appearance of the cartilage and unaffected thickness of the articular cartilage measured at five anatomically different points . Our results together with the published data on quinolone use in pediatrics suggest that ciprofloxacin does not cause arthropathy in humans. Ann Emerg Med, 1991 Oct, 20(10), 1131 - 4 Theophylline toxicity secondary to ciprofloxacin administration; Spivey JM et al.; We report the case of a 79-year-old woman who presented from a skilled nursing facility to the emergency department with signs and symptoms of theophylline toxicity and a serum theophylline concentration of 53.7 mg/L . The patient had been on a regular regimen of aminophylline for two months, with the addition of ciprofloxacin three days before arrival as the only identifiable potential cause of theophylline intoxication . She was monitored and treated conservatively with serial doses of activated charcoal, which resulted in a reduction of her serum theophylline level to a therapeutic concentration in 15 hours without adverse sequelae . The number of cases of theophylline intoxication secondary to concurrent ciprofloxacin administration is likely to increase, especially in nursing home populations, and it should be suspected when these patients present to the ED with the appropriate signs and symptoms . Management of theophylline intoxication should be based on clinical presentation as well as concentrations of the drug. Blood, 1991 Oct 1, 78(7), 1685 - 91 Enhanced repopulation of murine hematopoietic organs in sublethally irradiated mice after treatment with ciprofloxacin; Kletter Y et al.; We analyzed the effect of ciprofloxacin, fleroxacin, and ceftazidime on production of colony-stimulating factors (CSF) by cultured murine spleen cells in the presence of pokeweed mitogen (PWM) . Ciprofloxacin at concentrations of 5 to 10 micrograms/mL in concert with PWM stimulated CSF production by cultured spleen cells . A 3.5-fold increase in the number of CFU-C was observed in the presence of ciprofloxacin-PWM spleen conditioned medium (SCM) as compared with control cultures exposed to PWM-SCM only . Antimurine GM-CSF and antimurine interleukin-3 (IL-3) antibodies inhibited colony formation stimulated by PWM-SCM or ciprofloxacin-PWM-SCM . Fleroxacin and ceftazidime at concentrations of 1 to 100 micrograms/mL and ciprofloxacin at high concentration (greater than 10 micrograms/mL) either did not affect CSF production by spleen cells or had an inhibitory effect . In vivo treatment of sublethally irradiated (650 rad) mice with ciprofloxacin (15 mg/kg per dose three times daily for 5 days) resulted in an increased number of myeloid progenitors in the spleen and bone marrow (BM) of treated mice . In contrast, treatment with ceftazidime did not affect progenitor cell numbers . On days 4 and 8 postirradiation ciprofloxacin-treated mice had a 2.3- and 3.8-fold increase, respectively, in the number of CFU-C in the BM . The number of CFU-C in the spleen did not increase on day 4 postirradiation, but on day 8, the number increased 1.7-fold . On day 4 postirradiation, sublethally irradiated mice treated with ciprofloxacin had a higher WBC count, RBC count, and hemoglobin level as compared with ceftazidime- and saline-treated mice . Twenty-four days postirradiation, 45% of saline-treated mice (20 of 44), and 35% of ceftazidime-treated mice (8 of 23) died, as compared with 13% (5 of 38) of ciprofloxacin-treated mice (P less than .05) . These studies indicate that ciprofloxacin may have an immune-enhancing effect on the hematopoietic system in neutropenic mice. Mikrobiyol Bul, 1991 Oct, 25(4), 330 - 9 {The effects of ciprofloxacin and ofloxacin on the cellular and humoral immune response in mice}; Usluer G et al.; The effects of a 7 days chemotherapy with ciprofloxacin or ofloxacin on the cellular and humoral immune responses in albino mice were studied . The non-toxic doses of the drugs (10 or 30 mg/kg/day) were used . The delayed-type hypersensitivity reaction to sheep blood cells and skin biopsy were evaluated for cellular immune response . The complement fixation method was applied for the determination of the humoral immune response . Both drugs increased the cellular and humoral immune responses. Thorax, 1991 Oct, 46(10), 737 - 8 Mycobacterium fortuitum lung abscess treated with ciprofloxacin; Vadakekalam J et al.; Mycobacterium fortuitum rarely causes lung disease . Although treatment in the past has included intravenous antibiotics, this is the first report of a Mycobacterium fortuitum lung abscess that resolved with a prolonged course of oral ciprofloxacin alone . There is no evidence of recurrence 14 months after the end of treatment. Int J Artif Organs, 1991 Oct, 14(10), 634 - 8 Plasma exchange (PE) treatment in drug-induced toxic epidermal necrolysis (TEN); Sakellariou G et al.; Toxic epidermal necrolysis (TEN) or Lyell's syndrome is a rare fulminating skin disease notorious for its rapidly progressive course and high mortality rate . TEN is characterized by the sudden onset of epithelial necrosis of skin with frequently associated involvement of the gastrointestinal, genitourinary tract and bronchopulmonary linings . We describe the clinical course of five patients with severe drug-induced TEN, treated with PE . The suspected drugs were carbamazepine in one patient, paracetamol in one, a combination of paracetamol and mefenamic acid in one, allopurinol in one and ciprofloxacin in one . Three had a skin involvement affecting almost the entire surface of the body . In addition to the skin lesions, mouth, esophagus and lungs were also involved . Steroids proved ineffective . PE was carried out because of the rapid deterioration of the clinical picture . The mean number of PE sessions was 3.22 (range 1-5) . Complete remission of the syndrome was achieved in four patients . One patient died due to septic shock . As so far there is no treatment of proven value for this condition, controlled trials should be set up in order to assess the value of PE in TEN. Int J Clin Pharmacol Ther Toxicol, 1991 Sep, 29(9), 352 - 6 The distribution of ciprofloxacin and its metabolites in human plasma, pulmonary and bronchial tissues; Bacracheva N et al.; The disposition of ciprofloxacin and its pharmacologically active metabolites (sulfociprofloxacin, oxociprofloxacin, and desethylenciprofloxacin) in plasma, lung and bronchial tissues was studied in 24 patients undergoing a partial or total resection of the lung . The patients were divided into four groups, a control group and groups in which ciprofloxacin (200 mg) was given i.v . 1, 2 and 3 h before surgery . The concentrations of ciprofloxacin and its metabolites were determined by high performance liquid chromatography (HPLC) . Ciprofloxacin concentrations in lung tissue were four times and in bronchial tissue twice those in plasma (p less than 0.01) . The individual tissue concentrations of ciprofloxacin correlated with the individual plasma concentrations (r = 0.95 for lung; r = 0.94 for bronchi; p less than 0.001) . Metabolite concentrations in both tissues and plasma were 10- to 100-fold lower than the concentrations of ciprofloxacin . These data suggest that the concentrations of the parent compound are essential for the therapeutic efficacy of ciprofloxacin. J Pharmacol Exp Ther, 1991 Sep, 258(3), 1033 - 7 Enhanced entry of ciprofloxacin into the rat central nervous system induced by fenbufen; Naora K et al.; The effects of fenbufen on the transport of ciprofloxacin (CPFX) into the brain and cerebrospinal fluid (CSF) were investigated in rats . Periodically after a bolus i.v . dose of CPFX (10 mg/kg), alone or with fenbufen (20 mg/kg), to rats, aliquots of CSF and blood were collected and then the whole brain was readily excised from the animal after sacrifice by microwave irradiation . Serum levels of CPFX in the terminal phase were significantly elevated by the coadministration with fenbufen . However, the extent of CPFX binding to serum protein was not affected by fenbufen . Immediately after the coadministration with fenbufen, brain and CSF levels of CPFX were raised by about 15 to 70% and 70 to 100%, respectively . Both brain/serum unbound and CSF/serum unbound level ratios were increased by fenbufen at relatively early periods after drug injection . Analysis based on physiological models indicated that fenbufen significantly increased the apparent diffusion clearances of CPFX across blood-brain and blood-CSF barriers . These findings suggest that coadministered fenbufen may facilitate the entry of CPFX into the central nervous system not only by elevation of serum level but also by enhancement of permeability across the blood-brain or blood-CSF barrier. J Infect Dis, 1991 Sep, 164(3), 602 - 4 Ciprofloxacin treatment of drug-resistant falciparum malaria; Watt G et al.; A randomized, open study of high-dose ciprofloxacin (750 mg every 12 h) in uncomplicated falciparum malaria was conducted in Thailand . No patient completed the planned 1-week treatment course . Because of rising parasitemia (threefold higher at 36 h than on admission) and deterioration of clinical status, three individuals required quinine treatment 36 h after commencing ciprofloxacin; a fourth was given quinine at 54 h . The study was terminated early for safety reasons after only four ciprofloxacin and four control patients had been enrolled . Ciprofloxacin was well absorbed and efficiently entered erythrocytes; median plasma and red cell concentrations 90 min after the first dose were 4.0 (range, 3.7-6.8) and 5.1 (3.8-6.0) micrograms/ml, respectively . However, 50% inhibition of parasite growth in vitro required 6.6 micrograms/ml, (5.6-9.6) . Ciprofloxacin should not be used alone to treat chloroquine-resistant falciparum malaria. J Indian Med Assoc, 1991 Sep, 89(9), 257 - 9 Recent outbreak of chloramphenicol resistant typhoid fever in West Bengal; Sarkar AK et al.; Forty patients admitted with typhoid fever from 1-1-1990 to 31-3-1990 were studied . The clinical features differed from the classical clinical profile . Thirty cases (75%) did not respond to chloramphenicol . Gentamicin, nitrofurantoin, nalidixic acid, kanamycin, cephalexin and norfloxacin were tried according to the sensitivity pattern . But response was variable . Ciprofloxacin was used in 18 cases which failed to respond to one of the above drugs . The result was quite satisfactory with minimal side-effects. Tubercle, 1991 Sep, 72(3), 181 - 6 In vitro and in vivo activities of sparfloxacin (AT-4140) against Mycobacterium tuberculosis; Ji B et al.; The in vitro and in vivo activities of sparfloxacin (AT-4140) against M . tuberculosis are reported . The MICs of sparfloxacin for 50% and 90% of 18 clinical isolates were, respectively, 0.25 and 0.5 mg/l, one or two dilutions lower than that of ciprofloxacin and ofloxacin . In mice infected intravenously with 0.1 mg M . tuberculosis H37Rv strain, the minimal effective dosage of sparfloxacin, as assessed by survival rate, spleen enlargement and gross lung lesions, was 12.5 mg/kg . The activities of various regimens were in the following rank order: INH 25 mg/kg = sparfloxacin 50-100 mg/kg greater than ofloxacin 300 mg/kg greater than (or =) sparfloxacin 25 mg/kg greater than sparfloxacin 12.5 mg/kg greater than (or =) ofloxacin 200 mg/kg greater than ofloxacin 100 mg/kg greater than (or =) negative control . Therefore, on a weight to weight basis, sparfloxacin was six to eight-fold more active against M . tuberculosis infection in mice than ofloxacin . In addition, WIN 57273, a new broad-spectrum fluoroquinolone, at a dosage of 100 mg/kg daily, was inactive against M . tuberculosis infection. Jpn J Antibiot, 1991 Aug, 44(8), 839 - 45 {Clinical evaluation of ciprofloxacin in pulmonary infections in the patients with chronic respiratory diseases}; Kikuchi N et al.; The clinical efficacy of ciprofloxacin (CPFX) was investigated in pulmonary infections in patients with chronic respiratory diseases . Out of 58 cases collected, 54 were evaluable for utility of CPFX including 20 with pneumonia, 34 with chronic bronchial infection . CPFX was given orally at 200 mg 3 times per day . In 20 cases of pneumonia, the mean age was 62.0 years underlying diseases were chronic bronchitis 9, bronchiectasis 6, inactive pulmonary tuberculosis 4, and diffuse panbronchiolitis 1 . The efficacy rate of CPFX in this group was 90.0% . In 34 cases of chronic bronchial infection, the mean age was 59.8 years, underlying diseases included bronchiectasis 10, chronic bronchitis 8, inactive pulmonary tuberculosis 7, diffuse panbronchiolitis 5, and pulmonary emphysema 4 . The efficacy rate of CPFX in this group was 70.6% . The overall efficacy rate in the entire cases was 77.8%, and we consider CPFX to be effective in the treatment of patients with chronic respiratory diseases. Clin Pharmacol Ther, 1991 Aug, 50(2), 165 - 71 Comparison of the effect of temafloxacin, ciprofloxacin, or placebo on cerebral blood flow, glucose, and oxygen metabolism in healthy subjects by means of positron emission tomography; Bednarczyk EM et al.; STUDY OBJECTIVE: To determine the cause of the central nervous system effect of the fluorinated quinolones temafloxacin and ciprofloxacin by measuring cerebral blood flow and metabolism by use of positron emission tomography . DESIGN: This was a prospective, randomized, double-blind, placebo-controlled study . PATIENTS: The patients were 13 healthy, nonsmoking volunteers whose ages ranged from 18 to 40 years . RESULTS: We measured brain blood flow and metabolism by use of positron emission tomography before and after a five-dose course of 750 mg ciprofloxacin, 600 mg temafloxacin, or placebo given every 12 hours . Quinolone administration produced no significant effect on visual (qualitative) reading of the positron emission tomography scans . CONCLUSIONS: We conclude that short-term administration of temafloxacin, ciprofloxacin, or placebo does not significantly alter cerebral glucose or oxygen metabolism . Subjects treated with ciprofloxacin demonstrated a significant decrease in brain blood flow compared with baseline and with temafloxacin- or placebo-treated subjects. Chest, 1991 Aug, 100(2), 406 - 9 Pleural penetration of ciprofloxacin in patients with empyema thoracis; Morgenroth A et al.; We evaluated the pharmacokinetics of a single 200-mg dose of ciprofloxacin, administered as a 30-minute infusion, into pleural exudate in five elderly patients with empyema thoracis . Ciprofloxacin was measured by HPLC and the pharmacokinetic parameters were determined by noncompartmental methods . Mean peak serum levels 30 minutes after administration were 1.98 +/- 0.07 mg/L . Terminal serum half-lives ranged from 3.9 to 5.1 h . Mean concentrations of ciprofloxacin in pleural exudate were 1.44 +/- 0.42 mg/L at a mean time of 4.5 +/- 2.5 h . After this time, the pleural exudate level exceeded the corresponding serum twofold to tenfold . The mean percentage penetration into the inflammatory compartment was approximately 210 percent . Our data suggested that ciprofloxacin penetrates well into the pleural fluid of patients with empyema thoracis . The concentrations achieved were well above the MIC90 of most pathogens normally found in patients with empyema thoracis for a period of approximately 12 h. Clin Exp Immunol, 1991 Aug, 85(2), 331 - 4 Ciprofloxacin treatment in vivo increases the ex vivo capacity of lipopolysaccharide-stimulated human monocytes to produce IL-1, IL-6 and tumour necrosis factor-alpha; Bailly S et al.; Because in vitro treatment with quinolones, at pharmacological concentrations, modifies lipopolysaccharide (LPS) induced production of cytokines by monocytes, we studied the effect of orally administered ciprofloxacin (25 mg/kg) on the capacity of peripheral blood monocytes of healthy volunteers to produce tumour necrosis factor-alpha (TNF-alpha), IL-1 activity, IL-1 alpha, IL-1 beta and IL-6 ex vivo in response to endotoxin stimulation . After 7 days of ciprofloxacin, the extracellular and cellular production of TNF-alpha, the cellular production of IL-1 activity, the extracellular and cellular production of IL-1 alpha, and the cellular production of IL-6 increased significantly . Seven days after the end of the treatment, values returned to basal levels or even lower . To our knowledge, this is the first demonstration that ciprofloxacin can modulate in vivo the capacity of human monocytes to react to an inflammatory stimulus such as endotoxin. Cent Afr J Med, 1991 Aug, 37(8), 250 - 9 Therapeutic review: tuberculosis; Houston S et al.; Tuberculosis (TB) is increasing in Zimbabwe and other countries in Africa and world-wide . TB treatment and control face new difficulties including the impact of the HIV epidemic and drug resistance . There is now abundant evidence that six-month regimens are highly effective and, by improving compliance, can improve results and the cost-effectiveness of therapy . Intermittent therapy reduces drug costs and allows for the possibility of complete supervision . The optimal management of the HIV-infected TB patient has not yet been established but an increased rate of drug reactions suggests that standard treatment should be reassessedPIP: Each year, tuberculosis (TB) affects 10 million people and kills 3 million people all in the 15-53 year age group--the group which supports society economically and socially . It comprises the largest percentage of avoidable adult deaths (29%) in developing countries . The TB incidence is rising worldwide which, evidence indicates, is probably due to the HIV epidemic . Between mid-1988 to mid-1989, prevalence of HIV seropositivity among TB patients in Harare rose from 33% to 47% . Among the 20-40 year old male TB patients, 63.7% were HIV positive . Some evidence in Zimbabwe and elsewhere shows that TB responds well to standard treatment in most HIV positive patients . The most important public health measure against TB is to treat it with effective antibiotic regimens (95% relapse-free cure rates), but many TB treatments fail due to poor patient compliance . In fact, operational surveys of TB programs show that poor compliance is very common . Various forms of treatment include short course chemotherapy (6 months) and intermittent therapy (e.g., 2 doses each week) . Various TB antibiotics are isoniazid, rifampicin, INH, pyrazinamide, thiacetazone, streptomycin, and ethambutol . Some new possible antibiotics are emerging such as ansamycin and ciprofloxacin used to treat atypical mycobacteria . The Harare City Health Department in Zimbabwe has evidenced a 5-fold increase in the risk of a drug reaction in HIV infected TB patients . Thiacetazone and streptomycin were involved in 85% of these reactions . Antituberculosis treatment is costly in sub- Saharan Africa . Drug costs make up only 30% of the medical costs of outpatient treatment and only 5% for 1-2 months hospitalization . Nondrug costs include patient travel costs, time lost from work, and compromised job security and income . Thus developing countries should adopt the already known to be effective 6-month regimen for TB treatment . J Photochem Photobiol B, 1991 Aug, 10(3), 249 - 55 Phototoxic potential of quinolones; Cardenas AM et al.; The photohaemolytic potentials of the quinolones oxolinic acid, pipemidic acid, rosoxacin, norfloxacin, ciprofloxacin and M-193324 (synthesis intermediary) were evaluated and compared with the photohaemolysis induced by nalidixic acid . Quinolones with a piperazine group in position 7 (pipemidic acid, norfloxacin and ciprofloxacin) did not induce photohaemolysis . However, oxolinic acid, rosoxacin and M-193324 produced a concentration- and oxygen-dependent photohaemolysis . Ascorbic acid, histidine and thiourea inhibited the photohaemolysis induced by oxolinic acid, rosoxacin and M-193324, suggesting a photodynamic mechanism similar to that found with nalidixic acid . In addition, deuterium oxide increased the photohaemolysis induced by photohaemolytic quinolones, indicating that this process is mediated by singlet oxygen. Invest Ophthalmol Vis Sci, 1991 Jul, 32(8), 2388 - 92 The intravitreal penetration of orally administered ciprofloxacin in humans; Keren G et al.; To evaluate the penetration of ciprofloxacin, a new wide-spectrum oral antibiotic, into the vitreous, ciprofloxacin was administered orally to 21 patients who were scheduled to undergo vitreal surgery . Seven patients received 750 mg ciprofloxacin 4 hr before surgery (group I), seven patients received this dose 8 hr before surgery (group II), and seven patients received two 750-mg doses of oral ciprofloxacin every 12 hr . The last dose was administered 12 hr before surgery (group III) . Vitreous and blood samples were collected simultaneously and assayed for ciprofloxacin concentrations by bioassay and high-performance liquid chromatography. Antimicrob Agents Chemother, 1991 Jul, 35(7), 1484 - 5 Effects of enzyme supplementation on oral absorption of ciprofloxacin in patients with cystic fibrosis; Mack G et al.; The effect of pancreatic enzyme supplementation on the absorption of an oral dose of 250 mg of ciprofloxacin was studied in six patients with cystic fibrosis in a crossover design . The time to achieve maximum serum concentration was slightly reduced upon coadministration of pancreatic enzymes . There were no significant differences in peak concentration, elimination half-life, and area under the concentration-time curve. Infection, 1991 Jul-Aug, 19(4), 289 - 96 Safety of ciprofloxacin in children: worldwide clinical experience based on compassionate use . Emphasis on joint evaluation; Chysky V et al.; Six hundred and thirty four adolescents and children aged three days to 17 years treated with ciprofloxacin on a compassionate basis were analysed for drug safety . 62% of the ciprofloxacin courses were given to patients with respiratory tract infection, primarily those with acute pulmonary exacerbation of cystic fibrosis . The mean daily oral dose was 25.2 mg/kg body weight . The duration of treatment ranged from one to 880 days (mean 22.8 days) . Because of the arthropathogenic potential of quinolones in juvenile animals special emphasis was placed on the evaluation of musculoskeletal adverse events . Arthralgia considered by the treating physicians to be related to ciprofloxacin was reported in eight children, all of whom were females . Arthralgia resolved in all children . Some of these children were given subsequent courses of ciprofloxacin with no complaints of arthralgia . Overall, the safety profile of ciprofloxacin in children is not substantially different from that of adults. Drugs Aging, 1991 Jul-Aug, 1(4), 279 - 88 Quinolone disposition in the elderly . Practical implications; Nilsson-Ehle I et al.; The fluoroquinolones are antibiotics frequently used in infections that affect elderly individuals . The physiological aging process can profoundly affect the pharmacokinetics of drugs, necessitating adjustment of dosage regimens in the elderly . Changes in pharmacokinetics with age are mainly due to the progressive deterioration of renal function, with resultant lower clearance of drugs which are eliminated by the kidneys . Ofloxacin is almost totally renally excreted and elimination is slower in older age groups; a dose reduction is therefore recommended for this quinolone . Unexpected alterations in pharmacokinetics may occur, as exemplified by the increased bioavailability of oral ciprofloxacin in elderly subjects . This is a well-documented phenomenon of such significance that lower oral doses are advisable for the elderly . Renal clearance of ciprofloxacin decreases in old age, but because of substantial nonrenal elimination the total clearance is affected less . Studies of the pharmacokinetics of the other quinolones in old age are scarce . No data exist on the absolute oral bioavailability of norfloxacin, enoxacin and pefloxacin . Renal clearance seems to be reduced, but since no intravenous studies have been reported, the total and nonrenal clearances are unknown in the elderly . No safe conclusions can be drawn regarding the necessity of dose reductions from a pharmacokinetic point of view . However, reports of adverse reactions to quinolones in the elderly, especially concentration-dependent symptoms from the central nervous system, and the risk of interaction with other drugs, suggest the need for caution in determining dosages of all of these compounds in elderly subjects. Pharmacol Biochem Behav, 1991 Jul, 39(3), 587 - 9 The effect of ofloxacin and ciprofloxacin on pentylenetetrazol-induced convulsions in mice; Enginar N et al.; There have been several reports that convulsions, although rare, occur in patients who received fluoroquinolones . In this study, conducted for the evaluation of the convulsant action of fluoroquinolones, the effect of ofloxacin and ciprofloxacin on pentylenetetrazol-induced convulsions were investigated in mice . Mice were pretreated intraperitoneally (IP) with saline, ofloxacin (20 or 80 mg/kg) or ciprofloxacin (20 or 80 mg/kg) 30 minutes before subcutaneous (SC) administration of pentylenetetrazol (40 or 60 mg/kg) . In another experiment, diazepam (5 mg/kg) was injected (IP) in mice alone or in combination with ofloxacin (80 mg/kg) 30 minutes before pentylenetetrazol (40 mg/kg) administration (SC) . In each experiment mice were observed over the following hour for the incidence and onset of clonic convulsions . Results showed that both doses of ofloxacin increased the incidence of clonic convulsions induced by 40 mg/kg pentylenetetrazol . This effect, however was only significant in the higher dose and inhibited by diazepam . On the other hand, a similar proconvulsant effect by ciprofloxacin could not be demonstrated. J Assoc Physicians India, 1991 Jun, 39(6), 449 - 51 Preliminary observation on drug resistant cases of typhoid fever; Madan A et al.; We report here a sudden and marked increase in the occurrence, in a captive population, of typhoid fever cases showing multiple drug resistance . Fifty one cases of typhoid fever were seen from January '90 to June '90 of which 49% showed multiple drug resistance . Comparative figures for resistance in the previous three years were 0% (1987), 5% (1988), 14% (1989) . Shared resistance to chloramphenicol, ampicillin, amoxycillin and sensitivity to gentamicin, kanamycin, sisomycin, cephazolin, norfloxacin and ciprofloxacin in most of our cases suggest infection by a common strain with R-factor, mediated resistance . The illness was prolonged and associated with serious complications . Therapy with combination of quinolone derivatives and aminoglycoside antibiotics seemed justified on the basis of the in-vitro tests and clinical response . Efforts to identify the strain and stern public health measures to prevent further development of drug resistant S typhi are urgently indicated. Minerva Med, 1991 May, 82(5), 293 - 9 {Ciprofloxacin: a new fluoroquinolone for the treatment of respiratory tract infections}; Scarlini GF et al.; The Authors shortly present some statistical and epidemiological data on RTI and stress that these infections are nowadays the main infectious diseases . After an excursus of the most frequent infectious aetiologies, they show their experience in RTI treatment, mainly acute LRTI, with a new fluorquinolone, ciprofloxacin, at the posology of 250 mg p.o . b.i.d . or t.i.d., with good clinical results (90% of recovery) and excellent tolerability (absence of ADR in 100% of the treated patients). Indian J Pediatr, 1991 May-Jun, 58(3), 335 - 9 Ciprofloxacin in typhoid fever; Bavdekar A et al.; The study covers 78 children with typhoid fever who were hospitalized in April & May 1990 . Serious complications were present in 32% (toxemia 22%, ileus 25% and myocarditis 8%) . Blood cultures were positive in 30 of 49 tested . Others were diagnosed by positive Widal test . In vitro cultures of S . typhi were resistant to chloramphenicol (90%), ampicillin (93%) and co-trimoxazole (97%) . However all were highly sensitive to ciprofloxacin and moderately sensitive to cephalexin and gentamycin . Ciprofloxacin alone or in combination was given in 73 of the 78 children and found to be remarkably effective in controlling the disease and preventing relapse . No serious side effects were noted . The cohort is being followed up for possible long term adverse effects. Ther Drug Monit, 1991 May, 13(3), 263 - 7 Measurement of ciprofloxacin in human plasma, whole blood, and erythrocytes by high-performance liquid chromatography; Teja-Isavadharm P et al.; A simple, rapid, and accurate high-performance liquid chromatographic method using fluorescence detection is described for the measurement of ciprofloxacin in plasma, whole blood, and erythrocytes . Ciprofloxacin and the internal standard difloxacin were separated on a mu-Bondapak C18 column (30 cm x 3.9 mm inside diameter, 10 microns particle size), using a mobile phase of 0.1 M phosphate buffer (pH 2.5):acetonitrile (75:25, vol/vol) . The retention times were 5.1 min for ciprofloxacin and 7.9 min for difloxacin . The compounds were extracted from the three biological fluids using protein precipitation followed by a single-step liquid-liquid extraction . The assay is precise, with interassay coefficients of variation of less than or equal to 9.1% and an accuracy of less than or equal to 7.4% at 0.5 and 5.0 micrograms/ml (n = 5) . The mean extraction recoveries of ciprofloxacin in plasma, whole blood, and erythrocytes were 84.4, 63.9, and 48.0% . The limit of detection for ciprofloxacin is 25 ng/ml . Ciprofloxacin concentrations in the three biological fluids were measured in patients with uncomplicated falciparum malaria to demonstrate the application of the method. Pathol Biol (Paris), 1991 May, 39(5), 515 - 9 {Diffusion of ciprofloxacin into bronchial secretions in mechanically ventilated patients}; Saux P et al.; The aim of the study was to evaluate, in clinical conditions, the penetration of ciprofloxacin into bronchial secretions . Eight patients were included in the study . They presented with nosocomial pneumonia and were under controlled mechanical ventilation . Ciprofloxacin was given at a dose of 3 mg/kg over 30 min . Serial bronchial and blood samples were obtained over a 12 hour period on day 2 and 4 . Ciprofloxacin was measured by HPLC . Serum peak levels were 2.95 +/- 1 mg/l on day 2, and 2.43 +/- 0.7 mg/l on day 4 . Bronchial peak and through levels were 0.95 +/- 0.51 mg/l and 0.21 +/- 0.12 mg/l, respectively, on day 2, and 0.76 +/- 0.17 mg/l and 0.18 +/- 0.14 mg/l, respectively, on day 4 . The ratio of bronchial/serum peak was 0.32 +/- 0.11 and 0.33 +/- 0.06 on day 2 and 4, respectively . The ratio of AUC 0-12 h in the bronchial secretions/AUC 0-12 h in the serum samples was 0.66 +/- 0.04 and 0.55 +/- 0.27 on day 2 and 4, respectively. Antimicrob Agents Chemother, 1991 May, 35(5), 1014 - 6 Lack of ciprofloxacin ototoxicity after repeated ototopical application; Claes J et al.; The possible side effects of ototopically applied ciprofloxacin on inner ear function were investigated . The hearing function of pigmented guinea pigs was evaluated by daily frequency-specific evoked response audiometry after repeated application of the drug to both ears . Ciprofloxacin appeared to have no statistically significant effect on the hearing thresholds of the experimental animals. Antimicrob Agents Chemother, 1991 May, 35(5), 1004 - 7 Effect of staggered dose of calcium on the bioavailability of ciprofloxacin; Lomaestro BM et al.; The effect on ciprofloxacin's bioavailability (F) of calcium carbonate given 2 h before ciprofloxacin administration in 12 male volunteers was studied . The relative F with calcium was 0.98, maximum concentration of drug in serum increased significantly from 1.98 to 2.42 mg/liter (P = 0.039), and time to maximum concentration of drug in serum decreased from 1.82 to 1.26 h (P = 0.038) . Thus, a single calcium carbonate dose, administered 2 h before ciprofloxacin, does not alter the F of this quinolone. Hinyokika Kiyo, 1991 May, 37(5), 563 - 6 {Ciprofloxacin concentration in human prostatic tissue following 3 days' administration}; Morita M et al.; The penetration of Ciprofloxacin (CPFX) into the prostatic tissue and the serum was examined . Forty-four patients with benign prostatic hypertrophy treated with transurethral resection of the prostate were entered in this study . CPFX was administered orally in a dose of 200 mg three times daily for three days preoperatively . The blood samples were taken simultaneously at the time of the tissue sampling . The patients were divided into groups 1 and 2 . In group 1 (16 patients), the tissue sampling was done about 17 hours after the final drug administration . The mean concentration of CPFX was 0.61 +/- 0.40 microgram/g in the prostatic tissue and 0.27 +/- 0.19 micrograms/ml in the serum . In group 2 (28 patients), tissue sampling was done 5.5 hours after the final drug administration . The mean concentration of CPFX was 1.32 +/- 0.64 micrograms g in the prostatic tissue and 0.65 +/- 0.31 microgram/ml in the serum. JAMA, 1991 Mar 27, 265(12), 1563 - 5 Successful treatment of cat-scratch disease with ciprofloxacin; Holley HP Jr; Cat-scratch disease is usually a benign, self-limited disease . Infection may be asymptomatic but is commonly associated with painful regional lymphadenitis . Occasionally, disease may result in systemic symptoms and dissemination . Five adult patients, aged 24 to 57 years, were diagnosed as having cat-scratch disease, based on a positive history of cat scratches followed by typical symptoms including painful regional lymphadenitis, malaise, and positive cat-scratch skin tests . Diagnostic evaluations revealed no other cause for the lymphadenitis . Three patients had not received prior treatment with antibiotics, and two patients had failed to improve on other antibiotics . All five were treated with oral ciprofloxacin, 500 mg by mouth, twice daily . All patients had dramatic improvement in symptoms within a few days and none has relapsed during follow-up . This is the first report of successful treatment of cat-scratch disease with ciprofloxacin, which appears to be an effective therapy for cat-scratch disease in adults. South Med J, 1991 Apr, 84(4), 465 - 8 Seizures in patients simultaneously receiving theophylline and imipenem or ciprofloxacin or metronidazole; Semel JD et al.; Five patients had apparently drug-induced seizures while simultaneously receiving theophylline and either imipenem (three patients), ciprofloxacin (one patient), or ciprofloxacin and metronidazole (one patient) . Seizures ceased upon reduction in dosage or discontinuation of the suspected offending agents . Imaging studies failed to reveal new structural lesions in the central nervous system in any patient, and only one had a history of neurologic disease . Although the exact mechanism for seizure induction cannot be determined from these cases, potential drug interactions exist, because theophylline, imipenem, and ciprofloxacin are all believed to increase excitation of the central nervous system by inhibition of gamma-aminobutyric acid binding to receptors . In addition, ciprofloxacin decreases the clearance of theophylline from the body, predisposing the patient to elevated theophylline levels . Physicians prescribing theophylline with imipenem, ciprofloxacin, or metronidazole should carefully monitor patients for indications for drug therapy, drug dosage, organ impairment affecting drug metabolism, and signs of toxicity . Seizures may accompany oral theophylline therapy, even at "therapeutic" serum theophylline concentrations. Z Gastroenterol, 1991 Apr, 29(4), 143 - 5 {Ciprofloxacin-omeprazole combinatio