Arch Toxicol, 2000 Jan, 73(10-11), 564 - 72 Chondrotoxicity of ciprofloxacin in immature beagle dogs: immunohistochemistry, electron microscopy and drug plasma concentrations; Stahlmann R et al.; The systemic effects of ciprofloxacin in immature Beagles were studied . Dogs of 10-11 weeks were dosed orally for 5 days with 0 (n=3), 30 (n=5) and 200 (n=5) mg ciprofloxacin/kg body wt . Plasma concentrations were measured by high-performance liquid chromatography (HPLC) 1 h after dosing (assuming to be peak concentrations) . In view of the high doses used, the plasma concentrations were rather low and declined during the study period . For example, plasma concentrations in the high dose group were 6.6 +/- 0.9 mg/l (day 1), 3.9 +/- 1.4 mg/l (day 3), and 2.6 +/- 1.6 mg/l (day 5) . In control dogs and in dogs treated with the low dose of ciprofloxacin no pathological changes were seen by light microscopy . However, cleft formation and erosions were observed in joint cartilage from two of five dogs treated with 200 mg/kg . It is noteworthy that despite the high dose used cartilage lesions were not detectable in all five dogs of this group by light microscopy . Using antibodies against cell membrane receptors (e.g . the alpha(5)beta(1)-integrin) or matrix components (fibronectin, collagen II) the articular cartilage effects were studied in detail by immunohistochemistry . The most sensitive alteration was an increase in fibronectin which was detectable in the vicinity of the lesions in cartilage samples from the group of dogs administered the high dose . No clear-cut changes were seen with the use of antibodies against other matrix components . Electron microscopy revealed typical alterations in chondrocytes from dogs treated with ciprofloxacin: e.g., swollen mitochondria and enlarged rough endoplasmic reticulum . These changes were much more pronounced in dogs from the high dose group than in dogs from the low dose group . Our main conclusion is that after oral administration ciprofloxacin exhibits rather low chondrotoxicity, even in the most sensitive species known to date . This correlates with the findings in humans that ciprofloxacin seems to be less chondrotoxic than pefloxacin or other quinolones. Arch Toxicol, 2000 Jan, 73(10-11), 557 - 63 Ciprofloxacin causes cytoskeletal changes and detachment of human and rat chondrocytes in vitro; Egerbacher M et al.; Quinolones cause damage of articular cartilage in different species by forming chelate complexes with divalent cations and inducing magnesium deficiency . Cations are important for regular function of integrins, a group of transmembrane proteins which connect extracellular matrix proteins with the intracellular cytoskeleton . We have shown that cultivation of rat chondrocytes in ciprofloxacin (CFX)-supplemented and Mg(2+)-free medium led to pronounced changes in the cytoskeleton and decreased adhesion of cells to the culture dish . In order to test whether or not these effects are species-specific, we extended our studies on human chondrocytes . Human chondrocytes cultivated in CFX-supplemented medium (10, 40, 80 and 160 microg/ml) or Mg(2+)-free medium showed decreased ability to adhere to growth support, cell shape changes, and alterations in actin and vimentin cytoskeleton in a concentration dependent manner . Attachment of human chondrocytes to collagen type II coated cover slips was reduced to 90% in CFX group and 75% in Mg(2+)-free group on day 1 . This effect even increased after 4 days of culture in the respective medium (32% in CFX and 58% in Mg(2+)-free group) . We concluded that Mg(2+) deficiency is exerted via integrins, resulting in decreased ability to attach to extracellular matrix proteins and cytoskeletal changes . These effects are not species-specific . The attachment assay proves to be an easy to use experimental set-up to test ciprofloxacin and other quinolones for their chondrotoxic effects. Med Pediatr Oncol, 2000 Feb, 34(2), 87 - 91 Oral ciprofloxacin vs . intravenous ceftriaxone administered in an outpatient setting for fever and neutropenia in low-risk pediatric oncology patients: randomized prospective trial; Petrilli AS et al.; BACKGROUND: Infections are one of the major complications in children undergoing chemotherapy . Monotherapy with either ciprofloxacin or ceftriaxone is safe and efficient in low-risk patients (solid tumors and stage I/II lymphomas) . The same drugs may be used in an outpatient setting, decreasing costs and the risk of nosocomial infections . PROCEDURE: Low-risk patients (N = 70) with episodes of fever and neutropenia (N = 116) were randomized to receive either oral ciprofloxacin or intravenous ceftriaxone as outpatients . Only one patient had a central venous catheter . RESULTS: Episodes of fever and neutropenia were classified as fever of unknown origin (41% vs . 32%) or clinically documented infection (56% vs . 63%) in the ciprofloxacin and ceftriaxone groups, respectively . Most of these infections were of upper respiratory tract, skin, or gastrointestinal origin . The mean duration of neutropenia was 5 vs . 6 days . Fever persisted for 1-9 days (mean 2 vs . 3 days) . Therapy was successful with no modifications in 83% vs . 75% of the episodes . Patients were admitted in 7% vs . 4% of the episodes . No bone or joint side effects were seen in either group . All patients survived . CONCLUSIONS: Outpatient therapy with either oral ciprofloxacin or intravenous ceftriaxone for fever and neutropenia is effective and safe in pediatric patients with solid tumors and stage I/II non-Hodgkin lymphoma (low-risk patients) . Ophthalmology, 2000 Jan, 107(1), 72 - 5 One-year results of laser vision correction for low to moderate hyperopia; Williams DK; OBJECTIVE: To assess the efficacy and safety of hyperopic laser vision correction using a refined ablation architecture and the VISX STAR Excimer Laser . DESIGN: Prospective noncomparative case series . PARTICIPANTS: Fifty-two eyes with hyperopia from +1 to +6 diopters (D) spherical equivalent (SE) with or without cylinder < or =1.5 D based on cycloplegic refraction . Hyperopia was primary or caused by prior overcorrection of myopia . INTERVENTION: Hyperopic laser vision correction using a 9 mm/5 mm ablation profile and a pulse rate of 10 Hz . We prescribed ciprofloxacin and fluorometholone four times a day for 1 week . MAIN OUTCOME MEASURES: SE; uncorrected visual acuity (UCVA); predictability within +/- 0.5 D, +/- 1.0 D, and +/- 2.0 D of target refraction (emmetropia); loss of best-corrected visual acuity (BCVA); haze, and all complications at 1, 3, 6, and 12 months . RESULTS: We treated 52 eyes (mean preoperative SE; +3.03 D) . Forty-one eyes (78.8%) had primary hyperopia . At 3, 6, and 12 months, 66%, 67%, and 79% of all eyes had refraction within +/-0.5 D of emmetropia . At these same intervals, 83%, 88%, and 79% were within +/-1.0 D of emmetropia . At 12 months, all eyes were within +/-2.0 D . At 3 months, 85.4% of eyes had UCVA of 20/40 or better, with 95.3% achieving 20/40 or better at 6 months . At 1 year, all eyes (n = 19) had gained from 1 to 8 Snellen lines of UCVA, with most (n = 16) gaining between 3 and 7 lines . At 12 months, all eyes maintained preoperative BCVA or gained 1 to 4 lines . There was some early, transient haze < or = grade 1.5 . There were no corneal infiltrates, decentered ablations, or infections . CONCLUSIONS: These data suggest that the 9 mm/5 mm hyperopic ablation profile of the VISX STAR can produce accurate corrections without significant, progressive regression . Refractive stability was achieved 3 months after surgery . We did not observe any differences in outcomes between eyes treated for primary hyperopia and eyes treated for prior myopic overcorrections . We believe the quicker ablation time (10 Hz pulse rate) helped patients maintain fixation and reduced the risk of decentration . There was a high degree of satisfaction among all patients, especially those with presbyopia. Acta Trop, 2000 Jan 5, 74(1), 39 - 42 In vitro antimalarial activity of trovafloxacin, a fourth-generation fluoroquinolone; Hamzah J et al.; Trovafloxacin, a recently-developed fourth-generation fluoroquinolone, is more potent than other quinolone drugs against a wide range of organisms including Toxoplasma gondii . We assessed the in vitro antimalarial activity of trovafloxacin against three laboratory-adapted Plasmodium falciparum isolates and compared the results with those of ciprofloxacin and norfloxacin . Synchronous and asynchronous cultures were exposed to a range of drug concentrations, and growth inhibition was assessed using 3H-hypoxanthine incorporation . All isolates, both synchronous and asynchronous, exhibited comparable sensitivities with trovafloxacin (EC50 range, 1.8 x 10(-5) to 3.7 x 10(-5) mol/l) and ciprofloxacin (2.0 x 10(-5) to 3.9 x 10(-5) mol/l), but were less sensitive to norfloxacin (5.4 x 10(-5) to 6.6 x 10(-4) mol/l) . These results confirm that ciprofloxacin is twice as potent as norfloxacin against P . falciparum in vitro, but also show that trovafloxacin and ciprofloxacin have similar antimalarial potency . The EC50 concentrations of all three drugs were generally higher than those achieved after conventional doses in humans, suggesting that their clinical application may be limited to combination therapy . Recent reports of hepatotoxicity with trovafloxacin may also prevent the use of this drug in humans . However, newer fourth-generation quinolones may prove safer and have similar antimalarial potency. Int J STD AIDS, 1999 Dec, 10(12), 791 - 4 A retrospective study of the addition of ciprofloxacin to clarithromycin and ethambutol in the treatment of disseminated Mycobacterium avium complex infection; Keiser P et al.; Disseminated Mycobacterium avium complex (DMAC) infection is associated with increased morbidity and mortality in HIV-infected individuals . The combination antibiotic regimens containing clarithromycin can decrease symptoms and improve survival in patients with DMAC, however, optimal therapy remains to be defined . Quinolones have been widely used in the treatment of DMAC but their utility has not been established . A retrospective cohort study of DMAC infection was established in a metropolitan hospital providing comprehensive care to over 3000 HIV-infected individuals . Medical records of patients with DMAC diagnosed at the Parkland Memorial Hospital from 1991 to 1994 were reviewed for therapeutic regimens for DMAC, concomitant therapy for HIV and Pneumocystis carinii prophylaxis and date of death . Subjects were included if they were treated with clarithromycin and ethambutol . Cases were defined as those patients who received more than 30 days of ciprofloxacin as therapy for DMAC in addition to the other drugs that they received . The primary endpoint was the time to death from the data of DMAC diagnosis . Covariates effecting survival were analysed through the Cox proportional hazards model . Eighty-nine subjects with DMAC who were treated with clarithromycin and ethambutol were identified . Fifty-eight received ciprofloxacin in addition to clarithromycin and ethambutol . The time to death was significantly better in those subjects who were treated with ciprofloxacin than those who were not (489 days vs 281 days, P=0.01) . The sole significant predictor of improved survival on Cox proportional hazards model was ciprofloxacin therapy . Subjects treated with combination of clarithromycin, ethambutol and ciprofloxacin had improved survival over those treated with clarithromycin and ethambutol alone. JPEN J Parenter Enteral Nutr, 2000 Jan-Feb, 24(1), 42 - 8 Decreased in vitro fluoroquinolone concentrations after admixture with an enteral feeding formulation; Wright DH et al.; BACKGROUND: The purpose of this study was to determine if mixing of fluoroquinolones with a common enteral feeding formulation, Ensure (Ross Products Division, Abbott Laboratories, Columbus, OH), would alter the measured in vitro quinolone concentrations over a 24-hour period . METHODS: Tablets of ciprofloxacin (500 mg), levofloxacin (500 mg), and ofloxacin (300 mg) were crushed and mixed with 240 mL of Ensure, water and calcium chloride (500 mg/L), water and magnesium chloride (200 mg/L), water and calcium chloride and magnesium chloride, and water alone . Fluoroquinolone concentrations of the mixtures were measured, via high-performance liquid chromatography, at baseline and serially over 24 hours . Experiments were performed in duplicate, at three temperatures (5 degrees C, 25 degrees C, and 37 degrees C) . RESULTS: Average decreases of 82.5% +/- 1.5% for ciprofloxacin, 61.3% +/- 5.2% for levofloxacin, and 45.7% +/- 10.1% for ofloxacin (mean +/- 95% CI) were observed in vitro for Ensure over the two experimental sets at baseline . Serial analysis revealed no further significant change in any of the quinolone concentrations over the remaining 24-hour period . No significant decrease was noted with the quinolones when mixed in water and calcium, water and magnesium, water and calcium and magnesium, or water alone . This phenomenon appears to be unaffected by time and temperature . CONCLUSIONS: These data suggest there is an immediate and significant loss of fluoroquinolone when mixed with Ensure . An explanation for the loss of fluoroquinolone remains unclear. Mol Gen Mikrobiol Virusol, 1999, (4), 19 - 24 {Role of mutations in parC and gyrA in forming resistance of Mycoplasma hominis to fluoroquinolones}; Gushchin AE et al.; The set of the laboratory strain M . hominis H-34 mutants resistant to fluoroquinolones (ciprofloxacin-Cfl, lomefloxacin-Lfl, ofloxacin-Ofl) was obtained by selection in broth medium . The mutation was found in the quinolone resistance-determining region (QRDR) of A subunit of topoisomerase IV gene (parC) and new mutations were found in QRDR of genes encoding the A subunit of DNA gyrase (gyrA) in M . hominis mutants resistant to various concentrations of the Cfl, Lfl and Ofl . After multistep selection of the obtained mutants at constant concentrations of Cfl additional mutation Ser83 to Trp was revealed . No mutations in parE and gyrB were found . Mutations in parC for laboratory strain M . hominis H34 appeared at lower antibiotic concentrations than in gyrA . All mutations in gyr A were associated with mutations in parC . This confirms the previous data that topoisomerase IV is the primary target of Cfl and Ofl and suggests that it is the primary target of Lfl . Some M . hominis mutants selected at Ofl without any substitution in QRDRs were shown to be insensitive to Cfl and of Lfl . Studies of cross-resistance of the selected M . hominis mutants showed that their resistance to various fluoroquinolone concentrations could not depend on any mutations in QRDR of topoisomerase IV and DNA gyrase genes and suggests involvement of other unknown molecular mechanisms specific for Mycoplasmas. Cancer, 2000 Jan 1, 88(1), 180 - 5 A phase I study of gemcitabine and docetaxel in patients with metastatic solid tumors; Ryan DP et al.; BACKGROUND: A Phase I study was initiated to determine the maximum tolerated dose of weekly gemcitabine combined with monthly, fixed-dose docetaxel . METHODS: Patients with metastatic solid tumors were treated with docetaxel, 60 mg/m(2), on Day 1 every 28 days . Gemcitabine was administered on Days 1, 8, and 15 and underwent dose adjustment in cohorts of 3-6 patients . At the maximum tolerated dose, 11 additional patients were enrolled . RESULTS: Twenty-six patients received 85 cycles of therapy . At the first dose level, the planned gemcitabine dose on Days 1, 8, and 15 was 800 mg/m(2) . Two of the 6 patients treated at this dose level experienced dose-limiting toxicities (DLTs) requiring the reduction of gemcitabine to 600 mg/m(2) per dose and the administration of ciprofloxacin, 500 mg orally twice daily, on Days 8-18 . At the second dose level the first 3 patients experienced no DLTs and the dose of gemcitabine was increased to 700 mg/m(2) . Two of the 6 patients treated at the 700 mg/m(2) dose level experienced DLTs . Eleven additional patients were enrolled at the recommended Phase II dose of gemcitabine (600 mg/m(2)) . At this dose level, Grade 3/4 (according the National Cancer Institute's common toxicity criteria) neutropenia and thrombocytopenia occurred in 12.5% and 2.1% of cycles, respectively . Grade 3 and 4 nonhematologic toxicities were uncommon . Three of seven evaluable patients with pancreatic carcinoma had evidence of significant antineoplastic activity (three partial responses) . In addition, two complete responses (one patient with gastric carcinoma and one patient with ovarian carcinoma) and one partial response (patient with hepatocellular carcinoma) were noted in patients with other solid tumors . CONCLUSIONS: The regimen comprised of docetaxel, 60 mg/m(2), on Day 1 and gemcitabine, 600 mg/m(2), on Days 1, 8, and 15 with ciprofloxacin on Days 8-18 every 28 days is safe, well tolerated, and active . Dtsch Med Wochenschr, 1999 Dec 3, 124(48), 1453 - 5 {Malacoplakia: a possible complication of poorly controlled diabetes mellitus?}; Eichbauer-Sturm G et al.; HISTORY AND ADMISSION FINDINGS: A 47-year-old woman with poorly controlled diabetes mellitus (HbA1C 9.2%, fasting blood glucose > 200 mg/dl) had complained of moderately severe stabbing pain in the left abdomen . On admission there were no abnormal findings on abdominal palpation . INVESTIGATIONS: Abdominal ultrasound and computed tomography (CT) revealed a partly solid partly cystic well-circumscribed space-occupying lesion, about 15 cm in diameter, in the left abdomen, extending from the lower third of the kidney into the pelvis . DIAGNOSIS, TREATMENT AND COURSE: Biopsy of the lesion showed chronic granulating inflammation with foamy histiocytes (Hansemann macrophages) as characteristic substrate of extensive malakoplakia . Despite the size of the lesion it was not excised but long-term treatment with ciprofloxacin undertaken . At the same time, the diabetes was carefully controlled with ordinary insulin . Ten months later there was no longer any evidence of the lesion by ultrasound and CT . CONCLUSIONS: Even extensive malakoplakia can be successfully treated with ciprofloxacin . Poorly controlled diabetes together with a weak immune status (CD4/CD8 < or = 1) may have favoured the occurrence of malakoplakia. Br J Clin Pharmacol, 2000 Jan, 49(1), 32 - 8 The pharmacokinetics of oral fleroxacin and ciprofloxacin in plasma and sputum during acute and chronic dosing; Begg EJ et al.; AIMS: To examine the pharmacokinetics of ciprofloxacin and fleroxacin in plasma and sputum of patients with an acute exacerbation of chronic bronchitis or bronchiectasis following the first dose and again during the third day of treatment . METHODS: Twelve patients, aged >35 years, with acute infective exacerbation of bronchitis or bronchiectasis were allocated randomly to treatment with either fleroxacin 400 mg daily or ciprofloxacin 500 mg twice daily in an open, parallel group design . Plasma and sputum were collected during the first and third days of treatment . The time course of concentrations in sputum was modelled assuming that it acted as a negligibly small compartment of distribution . RESULTS: The mean sputum to plasma ratios of both ciprofloxacin and fleroxacin were approximately 1 on both days 1 and 3 . Peak concentrations of ciprofloxacin in sputum were achieved 1.6 (95% CI on mean difference 0.8-2.3) and 1.2 (0.4-1.9) h later than in plasma on day 1 and day 3, respectively (mean difference +/- 95% confidence interval) . For fleroxacin, the corresponding delay in time to peak concentrations was less marked and not significant . Fleroxacin accumulated in plasma (accumulation index 1.52+/-0.07) and sputum (accumulation index 1.79+/-0.39) from day 1 to day 3 . Accumulation did not occur for ciprofloxacin because the dose interval (12 h) was considerable longer than its half life (3-4 h) . CONCLUSIONS: The sputum to plasma ratio of ciprofloxacin and fleroxacin is approximately 1 . The time to peak concentrations of ciprofloxacin in sputum is slightly delayed compared with plasma . Fleroxacin accumulates over time in both plasma and sputum consistent with its longer half-life. J Laryngol Otol, 1999 Jul, 113(7), 663 - 5 When is a biopsy justified in a case of relapsing polychondritis? O'Connor Reina C, Garcia Iriarte MT, Barron Reyes FJ, Garcia Monge E, Luque Barona R, Gomez Angel D. Relapsing polychondritis (RP) is a relatively rare rheumatic condition of unknown aetiology . It is characterized by recurrent episodic inflammation of cartilaginous structures (nose, ear and trachea) . The clinical diagnosis of polychondritis can frequently be made with confidence in the absence of histological confirmation . A 61-year-old diabetic man, with bilateral relapsing aural inflammation, left ear deafness with tinnitus and pain at the sternocostal junctions is reported . After clinical diagnosis of relapsing polychondritis steroid therapy was started . An ear cartilage biopsy was performed confirming the clinical diagnosis . Subsequently soft tissue infection occurred at the operation site . The abscess was drained and oral ciprofloxacin was given with complete resolution of the infection over 30 days . As the infection is the main cause of death in these patients, we analyse whether biopsy is absolutely necessary for the diagnosis of RP in some patients. Antimicrob Agents Chemother, 2000 Jan, 44(1), 10 - 3 Ineffectiveness of topoisomerase mutations in mediating clinically significant fluoroquinolone resistance in Escherichia coli in the absence of the AcrAB efflux pump; Oethinger M et al.; Fluoroquinolone-resistant mutants, selected from a wild-type Escherichia coli K-12 strain and its Mar mutant by exposure to increasing levels of ofloxacin on solid medium, were analyzed by Northern (RNA) blot analysis, sequencing, and radiolabelled ciprofloxacin accumulation studies . Mutations in the target gene gyrA (DNA gyrase), the regulatory gene marR, and additional, as yet unidentified genes (genes that probably affect efflux mediated by the multidrug efflux pump AcrAB) all contributed to fluoroquinolone resistance . Inactivation of the acrAB locus made all strains, including those with target gene mutations, hypersusceptible to fluoroquinolones and certain other unrelated drugs . These studies indicate that, in the absence of the AcrAB pump, gyrase mutations fail to produce clinically relevant levels of fluoroquinolone resistance. Am J Hematol, 2000 Jan, 63(1), 28 - 31 Ciprofloxacin-warfarin coagulopathy: a case series; Ellis RJ et al.; Ciprofloxacin, when given to patients previously anticoagulated with warfarin, can occasionally cause an exaggerated hypoprothombinemic response and bleeding diatheses . Two such cases encountered at our institution are presented and data is combined with 64 cases reported to the Food and Drug Administration's (FDA) Spontaneous Reporting System (SRS) database, which included all cases reported from 1987 through 1997 . Of 66 total cases the median age was 72 (range 36-94) . The mean time to detection of the coagulopathy following the ciprofloxacin challenge was 5.5 days (n = 50) . Hospitalization was reported in 15 cases, bleeding in 25 cases, and death in one case . The median prothrombin time (PT) and International Normalized Ratio (INR) was 38.0 (n = 13) and 10.0 (n = 23), respectively . The mean number of medications taken was 6.5 (n = 45) . The mean time to correction was significantly shorter between the treated (2.5 days) and the untreated (4.0 days) groups (P < 0 . 008) . The ciprofloxacin-warfarin coagulopathy occurred most commonly in patients in their seventh decade and in those who require polypharmacy . Active treatment of the coagulopathy results in more rapid resolution than observation alone . Clinicians should be aware of the potential bleeding complications that can occur with the ciprofloxacin-warfarin drug-drug interaction . J Agric Food Chem, 1999 Jul, 47(7), 2963 - 8 Immunosorbents coupled on-line with liquid chromatography for the determination of fluoroquinolones in chicken liver; Holtzapple CK et al.; Four fluoroquinolones were analyzed in fortified chicken liver using an automated, on-line immunoaffinity extraction method . The fluoroquinolones were extracted from the liver matrix using an immunoaffinity capture column containing anti-sarafloxacin antibodies covalently cross-linked to protein G . After interfering liver matrix components had been washed away, the captured fluoroquinolones were automatically eluted directly onto a reversed phase column . Liquid chromatographic analyses were performed by isocratic elution using 2% acetic acid/acetonitrile (85:15) as the mobile phase and an Inertsil phenyl column with fluorescence detection at excitation and emission wavelengths of 280 and 444 nm, respectively . No significant interferences from the sample matrix were observed, indicating good selectivity with the immunoaffinity column . Overall recoveries from fortified liver samples (20, 50, and 100 ng/g) ranged between 85.7 and 93.5% with standard deviations of <5% . The limit of quantification for each fluoroquinolone was 1 ng/mL . The limits of detection, based on a signal-to-noise ratio of 5:1, were 0.47, 0.32, 0.87, and 0.53 ng/mL for ciprofloxacin, enrofloxacin, sarafloxacin, and difloxacin, respectively. Drugs, 1999, 58 Suppl 2, 37 - 42 Toxicity of quinolones; Stahlmann R et al.; Reactions of the gastrointestinal tract, the CNS and the skin are the most often observed adverse effects during therapy with fluoroquinolones . At least for some of the newer fluoroquinolones a steep dose-response relationship of adverse effects seems to exist . Pathogenesis of the neurotoxic effects of fluoroquinolones is still unknown . Among the newer drugs, trovafloxacin caused mild CNS reactions such as dizziness and lightheadedness in a considerable proportion of patients . Young females seem to be especially sensitive to this effect, which diminishes during treatment or if taken together with food . Cardiotoxic potentials of sparfloxacin and grepafloxacin are higher than those of other fluoroquinolones, but during therapy no clearcut drug-related serious reactions have been reported, apart from a slight prolongation of the QT interval . However, to avoid risks these drugs should not be prescribed to patients with known prolongation of the QT interval (e.g . patients on antiarrhythmics) . Phototoxicity has been described for all quinolones, but derivatives with a halogen atom at position 8 show the highest potential for such reactions . Fleroxacin, sparfloxacin, clinafloxacin and lomefloxacin belong to this group of fluoroquinolones . The phototoxic potential of the other new fluoroquinolones is considerably lower, but extensive exposure to UV light should generally be avoided during therapy with all quinolones . Chondrotoxicity of quinolones, as observed in immature animals, can affect articular cartilage and/or the epiphyseal growth plate, depending on the developmental stage . Pathogenesis of chondrotoxicity can probably be explained by the magnesium-chelating properties of these drugs . As juveniles are especially sensitive, use of these drugs in paediatrics should be restricted to carefully selected indications (such as the use of ciprofloxacin in cystic fibrosis) . Another manifestation of the toxic effects of quinolones on connective tissue structures are tendopathies . Tendinitis and tendon ruptures have occurred as late as several months after quinolone treatment . Overall, quinolones are well tolerated drugs . Their specific toxic potentials have to be considered when they are chosen for treatment of bacterial infections. Biosci Rep, 1999 Aug, 19(4), 293 - 300 Role of an ABC importer in mycobacterial drug resistance; Chakraborti PK et al.; Phosphate specific transporter (Pst) in bacteria is involved in phosphate transport . Pst is a multisubunit system which belongs to the ABC family of transporters . The import function of this transporter is known to be operative at media phosphate concentrations below the millimolar range . However, we found amplification of this transporter in a laboratory generated ciprofloxacin resistant Mycobacterium smegmatis colony (CIPr) which was grown in a condition when phosphate scavenging function of this operon was inoperative . Our results therefore argue the role of this ABC importer in conferring high level of fluoroquinolone resistance in CIPr. Clin Pharmacokinet, 1999 Nov, 37(5), 361 - 84 Clinical pharmacokinetics of mexiletine; Labbe L et al.; Mexiletine, a class Ib antiarrhythmic agent, is rapidly and completely absorbed following oral administration with a bioavailability of about 90% . Peak plasma concentrations following oral administration occur within 1 to 4 hours and a linear relationship between dose and plasma concentration is observed in the dose range of 100 to 600 mg . Mexiletine is weakly bound to plasma proteins (70%) . Its volume of distribution is large and varies from 5 to 9 L/kg in healthy individuals . Mexiletine is eliminated slowly in humans (with an elimination half-life of 10 hours) . It undergoes stereoselective disposition caused by extensive metabolism . Eleven metabolites of mexiletine are presently known, but none of these metabolites possesses any pharmacological activity . The major metabolites are hydroxymethyl-mexiletine, p-hydroxy-mexiletine, m-hydroxy-mexiletine and N-hydroxy-mexiletine . Formation of hydroxymethyl-mexiletine, p-hydroxy-mexiletine and m-hydroxy-mexiletine is genetically determined and cosegregates with polymorphic debrisoquine 4-hydroxylase {cytochrome P450 (CYP) 2D6} activity . On the other hand, CYP1A2 seems to be implicated in the N-oxidation of mexiletine . Various physiological, pathological, pharmacological and environmental factors influence the disposition of mexiletine . Myocardial infarction, opioid analgesics, atropine and antacids slow the rate of absorption, whereas metoclopramide enhances it . Rifampicin (rifampin), phenytoin and cigarette smoking significantly enhance the rate of elimination of mexiletine, whereas ciprofloxacin, propafenone and liver cirrhosis decrease it . Cimetidine, ranitidine, fluconazole and omeprazole do not modify the disposition of mexiletine . Conversely, mexiletine is known to alter the disposition of other drugs, such as caffeine and theophylline . Factors affecting the elimination of mexiletine may be clinically important and dosage adjustments are often necessary. Am J Vet Res, 1999 Nov, 60(11), 1377 - 82 Pharmacokinetic variables and tissue residues of enrofloxacin and ciprofloxacin in healthy pigs; Anadon A et al.; OBJECTIVES: To determine pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after a single i.v . and i.m . administration of enrofloxacin and tissue residues after serial daily i.m . administration of enrofloxacin in pigs . ANIMALS: 20 healthy male pigs . PROCEDURE: 8 pigs were used in a crossover design to investigate pharmacokinetics of enrofloxacin after a single i.v . and i.m . administration (2.5 mg/kg of body weight) . Twelve pigs were used to study tissue residues; they were given daily doses of enrofloxacin (2.5 mg/kg, i.m . for 3 days) . Plasma and tissue concentrations of enrofloxacin and ciprofloxacin were determined . Residues of enrofloxacin and ciprofloxacin were measured in fat, kidney, liver, and muscle . RESULTS: Mean (+/-SD) elimination half-life and mean residence time of enrofloxacin in plasma were 9.64+/-1.49 and 12.77+/-2.15 hours, respectively, after i.v . administration and 12.06+/-0.68 and 17.15+/-1.04 hours, respectively, after i.m . administration . Half-life at alpha phase of enrofloxacin was 0.23+/-0.05 and 1.94+/-0.70 hours for i.v . and i.m . administration, respectively . Maximal plasma concentration was 1.17 +/-0.23 microg/ml, and interval from injection until maximum concentration was 1.81+/-0.23 hours . Renal and hepatic concentrations of enrofloxacin (0.012 to 0.017 microg/g) persisted for 10 days; however, at that time, ciprofloxacin residues were not detected in other tissues . CONCLUSIONS AND CLINICAL RELEVANCE: Enrofloxacin administered i.m . at a dosage of 2.5 mg/kg for 3 successive days, with a withdrawal time of 10 days, resulted in a sum of concentrations of enrofloxacin and ciprofloxacin that were less than the European Union maximal residue limit of 30 ng/g in edible tissues. Am J Gastroenterol, 1999 Nov, 94(11), 3197 - 201 Long-term ciprofloxacin treatment for the prevention of biliary stent blockage: a prospective randomized study; Sung JJ et al.; OBJECTIVE: In vitro experimental and animal studies have shown that quinolones reduce the adherence of bacteria on a polyethylene tube and prevent stent blockage . Our aim was to see whether ciprofloxacin prevents stent blockage in patients with malignant stricture of the biliary tract . METHODS: Patients with inoperable biliary or pancreatic tumor not involving the bifurcation of the common hepatic duct were recruited . They were randomized to receive either endoscopic stenting alone or stenting with prophylactic treatment of ciprofloxacin (200 mg i.v . before stenting, followed by 250 mg orally twice per day) . In each follow-up visit, clinical symptoms of cholangitis were documented and blood samples taken for blood counts, serum levels of bilirubin, and alkaline phosphatase . Stent blockage was defined as clinical symptom(s) of cholangitis with biochemical or radiological evidence of stent dysfunction . RESULTS: Fifty-eight patients were recruited into the study . Three patients in the stenting group and three in the ciprofloxacin group were excluded after randomization . Eleven patients received stenting alone and five patients receiving ciprofloxacin had previous endoscopic stenting . Thirteen patients (50%) in the ciprofloxacin group and eight patients (31%) in the stenting group died before stent blockage . Ten patients (38%) in each group had stent blockage during the follow-up at 20 wk . The median stent patency was 11.6 wk and 11.9 wk in the ciprofloxacin group and the stenting group, respectively . Kaplan-Meier analysis of stent patency showed no difference between the two groups . Among patients who received endoscopic stenting for the first time, there was a trend favoring ciprofloxacin treatment, but the difference was not significant . The 30-day and 20-wk mortality between the groups were comparable . CONCLUSION: Long-term use of ciprofloxacin does not prevent blockage of polyethylene biliary stents. Am J Respir Crit Care Med, 1999 Nov, 160(5 Pt 1), 1611 - 6 The spectrum of mycobacterial infection after lung transplantation; Malouf MA et al.; Despite the success of lung transplantation, infection is one of the leading causes of morbidity and mortality . Mycobacterial infections have been reported rarely, with the majority due to Mycobacterium tuberculosis . Our aim was to assess the incidence, etiology, and clinical outcome of mycobacterial infection after lung transplantation; to do so, we have studied retrospectively all lung and heart- lung transplants performed over a 12-yr period between November 1986 and June 1998 (n = 261) . Twenty-three patients (9%) (M:F, 11:12) were diagnosed with mycobacterial infections in 25 sites, including n = 19, pulmonary (M . avium complex {n = 13}, M . tuberculosis {n = 2}, M . abscessus {n = 2}, M . asiaticum {n = 1}, and M . kansasii {n = 1}) and n = 6 extrapulmonary (M . haemophilum {n = 5} and M . abscessus {n = 1}) infections . Time to diagnosis from transplantation was 677 +/- 735 d (range, 2- 3,086 d) . Three episodes of transient colonization with M . avium were not treated; the remaining (22 of 25, 88%) were treated . Initial baseline therapy for nontuberculous mycobacteria included clarithromycin, rifampicin, ciprofloxacin, and/or ethambutol . All cutaneous lesions resolved completely, while clinical and graft function improved in 11 of 16 (69%) and 8 of 16 (50%) of patients treated, respectively . Seventeen of 23 patients (72%) survived at a follow-up of 1,658 +/- 759 d (range, 522-3,285 d) . Complications, predominantly due to rifampicin, included gastrointestinal intolerance and an increased tendency for rejection . There were no deaths attributable to mycobacterial disease or therapy . We conclude that mycobacterial infection, particularly due to nontuberculous mycobacteria, is relatively common after lung transplantation and may be an unrecognized cause of graft dysfunction . Early treatment of cutaneous lesions is associated with excellent control; however, graft dysfunction may be permanent . Although drug toxicity and interactions with immunosuppressive agents were not infrequent, the majority of these infections can be managed successfully. Clin Nucl Med, 1999 Nov, 24(11), 855 - 8 Cold-hot mismatch between Tc-99m HMPAO-labeled leukocytes and Tc-99m ciprofloxacin in axial skeleton infections: a report of three cases; Amaral H et al.; Radiolabeled leukocyte scintigraphy is a well-established technique for the diagnosis of inflammation and infection with a typical presentation of a hot spot within the abnormal areas . However, in some cases of osteomyelitis of the axial skeleton, a cold defect pattern has been described . Tc-99m ciprofloxacin is a new agent claimed to be specific for imaging sites containing viable bacteria . In this report, we present three cases of proved bacterial infection of the axial skeleton with a mismatch pattern between Tc-99m ciprofloxin and tagged leukocytes . Although Tc-99m-labeled leukocyte scanning showed a cold defect, probably caused by bone marrow replacement, the Tc-99m ciprofloxacin consecutively revealed a hot spot at the site of infection . These data suggest that Tc-99m ciprofloxacin should be a better agent than radiolabeled leukocytes for detecting osteomyelitis of the axial skeleton. Antimicrob Agents Chemother, 1999 Nov, 43(11), 2710 - 5 Mechanisms of fluoroquinolone transport by human neutrophils; Walters JD et al.; Neutrophils accumulate ciprofloxacin and other fluoroquinolones, a process that enhances the killing of intracellular pathogens and could facilitate the delivery of these agents to infection sites by migrating neutrophils . The mechanisms by which transport occurs have not been characterized . In the present study, quiescent neutrophils transported ciprofloxacin with an observed K(m) of 167 microgram/ml (501 microM) and a maximum velocity of 25.2 ng/min/10(6) cells . When neutrophils were stimulated with phorbol myristate acetate (PMA), a second component of ciprofloxacin transport was induced . This pathway had an apparent K(m) of 9.76 microgram/ml (29.3 microM) and a maximum velocity of 59.3 ng/min/10(6) cells . Transport by both pathways was Na(+) independent . Ciprofloxacin transport by quiescent cells was relatively insensitive to pH and N-ethylmaleimide but was competitively inhibited by adenine (K(i) = 1.55 mM) . Papaverine, a benzylisoquinoline known to inhibit nucleobase transport, also inhibited ciprofloxacin transport by quiescent cells . In contrast, transport by PMA-stimulated cells was enhanced at pH 8.2, inhibited at pH 6.2, and blocked by N-ethylmaleimide . Cationic and neutral amino acids and cystine competitively inhibited ciprofloxacin transport by PMA-stimulated neutrophils (K(i) = 158 microM for ornithine) but had little effect on quiescent cells . PMA-activated transport was not inhibited when the Na(+) in the medium was replaced with K(+) or Li(+), and the pattern of inhibition by cationic and neutral amino acids was similar . In summary, neutrophils continuously transport ciprofloxacin via a transport pathway shared by adenine . Activation by PMA induces a separate, higher-affinity transport pathway shared by a broad scope of amino acids . Neutrophils utilize one or both of these mechanisms to transport other fluoroquinolones. Drug Metab Dispos, 1999 Nov, 27(11), 1225 - 31 Correlation between in vivo and in vitro hepatic uptake of metabolic inhibitors of cytochrome P-450 in rats; Yamano K et al.; To predict the degree of accumulation of hepatic metabolic inhibitors in the liver from the in vitro data, we investigated the relationship between cell/medium concentration ratios (C/M ratios) in isolated rat hepatocytes and liver/blood unbound concentration (K(Bf)) after i.v . administration of various metabolic inhibitors such as itraconazole, ketoconazole, verapamil, diltiazem, enoxacin, ciprofloxacin, clarithromycin, cimetidine, and nizatidine . The C/M ratios of itraconazole were approximately 6,000 and 200 at the concentrations of 0.1 and 10 microg/ml, respectively, and the uptake of ketoconazole and verapamil into the hepatocytes also showed a concentration dependence, although the degree was smaller than that of itraconazole . The uptake of diltiazem, enoxacin, ciprofloxacin, and clarithromycin into the hepatocytes showed linear profiles on concentration dependence . There was an excellent correlation between C/M ratios and K(Bf) values of all nine drugs with a slope of 1 . This finding suggested the possibility of predicting drug concentrations in the liver (C(H)) from C/M ratios, the blood concentrations of drugs (C(B)) and unbound fraction in blood (f(B)), which was expressed by C(H) = (C/M) . C(B) . f(B) . It may be possible to predict the drug concentrations in human liver from K(Bf) values estimated with isolated human hepatocytes and concentrations in the blood in a similar manner as in rats. Lancet, 1999 Oct 16, 354(9187), 1327 - 30 Effectiveness of therapeutic plasma exchange in the 1996 Lanarkshire Escherichia coli O157:H7 outbreak; Dundas S et al.; BACKGROUND: The largest number of adult cases of haemolytic uraemic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP) during an Escherichia coli O157 outbreak occurred in 1996 in central Scotland . Adults who develop HUS/TTP induced by E . coli O157 tend to be elderly and have a historical mortality rate of almost 90% when treated conservatively . Therefore the decision was made to treat adults who developed HUS/TTP during this outbreak with therapeutic plasma exchange (TPE) . We report our outcome with this controversial treatment . METHODS: A case definition for HUS/TTP was developed at the beginning of the outbreak . All cases meeting this definition were considered for TPE . Information on demographics, clinical features, treatment and outcome of patients was obtained by retrospective case note review . FINDINGS: 22 adults developed HUS/TTP . They had a mean age of 71 years . 16 cases received TPE . Six cases had contraindications to TPE or died before the procedure could be done . Ten of the 22 (45%) adults with HUS/TTP died . Five of the 16 (31%) TPE-treated cases died, four of eight aged over 70 years compared with one of eight aged less than 70 years . Premorbid illness, neurological features, treatment with ciprofloxacin or prostacyclin, and the laboratory severity of HUS/TTP were not associated with death; the number of cases, however, was too small to allow statistical conclusion . INTERPRETATION: The mortality rate is high in adults who develop HUS/TTP induced by E . coli O157 . TPE appears to be a promising treatment that was well tolerated in our elderly patients . A national register of adult cases of HUS/TTP induced by E . coli O157 should be established. Eur J Gastroenterol Hepatol, 1999 Oct, 11(10), 1121 - 7 Epidemiological and clinical features of Spanish patients with Crohn's disease . Spanish Epidemiological and Economic Study Group on Crohn's disease; Drug treatment of common STDs: part I . Herpes et al.; West Virginia University Hospitals, Morgantown 26506-8045, USAIn 1998, the Centers for Disease Control and Prevention released guidelines for the treatment of sexually transmitted diseases . Several treatment advances have been made since the previous guidelines were published . Part I of this two-part article describes current recommendations for the treatment of genital ulcer diseases, urethritis and cervicitis . Treatment advances include effective single-dose regimens for many sexually transmitted diseases and improved therapies for herpes infections . Two single-dose regimens, 1 g of oral azithromycin and 250 mg of intramuscular ceftriaxone, are effective for the treatment of chancroid . A three-day course of 500 mg of oral ciprofloxacin twice daily may be used to treat chancroid in patients who are not pregnant . Parenteral penicillin continues to be the drug of choice for treatment of all stages of syphilis . Three antiviral medications have been shown to provide clinical benefit in the treatment of genital herpes: acyclovir, valacyclovir and famciclovir . Valacyclovir and famciclovir are not yet recommended for use during pregnancy . Azithromycin in a single oral 1-g dose is now a recommended regimen for the treatment of nongonococcal urethritis. J Pharm Sci, 1999 Oct, 88(10), 1036 - 40 Development of an in vitro dissolution method using microdialysis sampling technique for implantable drug delivery systems; Dash AK et al.; The major challenge faced during the development of implantable dosage forms for site-specific delivery is monitoring the local concentration of the drug at or around the site of action . The tissue concentration at the site is generally measured by either sacrificing the animal at different points in time or by determining the amount of drug left in the implants at various time intervals . Unfortunately, there are no official in vitro dissolution methods available to study the release characteristics of drugs from this drug delivery system . The objective of this investigation was to develop a simple method using microdialysis sampling technique to serve as an in vitro dissolution method for implantable drug delivery systems . Ciprofloxacin implants were prepared by compressing ciprofloxacin microcapsules in poly(lactic acid) (PLA) and poly(lactic-glycolic acid) (PLGA) . A sensitive HPLC method was developed and validated for the assay of Ciprofloxacin . An in vitro dissolution method was developed to study the release characteristics of drug from these implants . The method used a microdialysis sampling technique and a small sample volume of release medium . The various advantages and disadvantages of this method over other USP methods are discussed. Drug Saf, 1999 Oct, 21(4), 311 - 23 Treating inflammatory bowel disease during pregnancy: risks and safety of drug therapy; Connell W et al.; The safety of drug therapy for inflammatory bowel disease during pregnancy is an important clinical concern . Current available information is largely derived from animal studies and clinical experience among patients with inflammatory bowel disease and autoimmune disorders and organ transplant recipients . However, these data are confounded by various factors including difficulty projecting the results of animal studies to humans, methodological deficiencies of some studies, insufficient experience with certain agents, difficulty distinguishing the fetal effects of underlying disease from drug therapy and a need to consider the impact of background rates of adverse fetal outcomes which apply to all pregnancies . In inflammatory bowel disease, the effects of active inflammation on the fetus are believed to be more harmful than those of drug treatment, and therapy is often justified to induce or maintain remission during pregnancy . The choice of appropriate treatment is determined by the severity of the disease and the potential for drug toxicity . No causal relationship has been established between exposure to sulfasalazine or other 5-aminosalicylic acid drugs and the development of congenital malformations . These drugs may be used with relative safety during pregnancy and lactation . Considerable experience with corticosteroids have shown them to pose very small risk to the developing fetus . Current evidence indicates that maternal use of azathioprine is not associated with an increased risk of congenital malformations, though impaired fetal immunity, growth retardation or prematurity is occasionally observed . Preliminary evidence derived from patients with inflammatory bowel disease show no significant fetal toxicity following first trimester exposure to mercaptopurine, though its elective use in pregnancy is controversial . Cyclosporin is not teratogenic, but may be associated with growth retardation and prematurity . Pregnancy should be avoided in women treated with methotrexate because of its known abortifacient effects and risk of causing typical malformations . Although treatment with metronidazole or ciprofloxacin for short durations appear to be devoid of adverse fetal reactions, the effect of prolonged exposure as required in Crohn's disease remains unknown. Arthritis Rheum, 1999 Sep, 42(9), 1894 - 7 Ciprofloxacin treatment does not influence course or relapse rate of reactive arthritis and anterior uveitis; Wakefield D et al.; OBJECTIVE: To assess the efficacy of ciprofloxacin in the treatment of reactive arthritis (ReA) and anterior uveitis (AU) in a double-blind, randomized, placebo-controlled trial . METHODS: Seventy-two patients participated in this study, 56 with ReA and 42 with AU (26 patients had both ReA and AU) . Ciprofloxacin (750 mg twice a day) was administered for 12 months with a 12-month followup . End points of the study included time to disease relapse and measures of disease severity . RESULTS: There was no difference between groups in time to disease relapse, joint inflammation, number of joints and enthesis involved in patients with ReA, or signs and symptoms of AU . CONCLUSION: Long-term treatment of ReA and AU with ciprofloxacin made no statistically significant difference to the natural history of these diseases or their severity. Hear Res, 1999 Oct, 136(1-2), 165 - 8 Aminoglycosides activate oxygen metabolites production in the cochlea of mature and developing rats; Lopez-Gonzalez MA et al.; The ototoxicity of antibiotics, particularly of aminoglycosides, is a well-known undesirable side effect which may be based on a free radical mechanism . We studied the effect of different antibiotics in the production of reactive oxygen species in freshly isolated cochleas of mature and 2-10 weeks old developing rats . Phorbol myristate acetate induced the release of reactive oxygen species after a lag time close to 30 s and declined back to basal values in 10-20 min . The rate of reactive oxygen species production correlated inversely to the age in 2-10 weeks old rats . The study of a set of antibiotics showed that a very low concentration of gentamicin and streptomycin (10-100 ng/ml) enhanced the effect of phorbol myristate acetate . At the above-indicated concentrations, ciprofloxacin did not modify phorbol myristate acetate-induced activation . These results show the enhancement by aminoglycosides of reactive oxygen species production in cochlear tissues, particularly in developing rats. Antimicrob Agents Chemother, 1999 Oct, 43(10), 2571 - 3 In vitro susceptibilities of Mycoplasma hominis to six fluoroquinolones as determined by E test; Waites KB et al.; Twenty isolates of Mycoplasma hominis were tested for their susceptibility to six fluoroquinolones by the E test . The MICs at which 90% of the isolates were inhibited (in micrograms per milliliter) were as follows: sparfloxacin, 0.031; clinafloxacin, moxifloxacin, and trovafloxacin, 0.063; levofloxacin, 0.25; and ciprofloxacin, 0.5 . Increasing the amount of inoculum or incubation in CO(2) elevated MICs by </=1 dilution . E tests produce fluoroquinolone MICs comparable to those obtained by agar and microbroth dilution for M . hominis. J Pharm Pharmacol, 1999 Aug, 51(8), 905 - 10 Prediction of clearance, volume of distribution and half-life by allometric scaling and by use of plasma concentrations predicted from pharmacokinetic constants: a comparative study; Mahmood I; Pharmacokinetic parameters (clearance, CL, volume of distribution in the central compartment, VdC, and elimination half-life, t1/2beta) predicted by an empirical allometric approach have been compared with parameters predicted from plasma concentrations calculated by use of the pharmacokinetic constants A, B, alpha and beta, where A and B are the intercepts on the Y axis of the plot of plasma concentration against time and alpha and beta are the rate constants, both pairs of constants being for the distribution and elimination phases, respectively . The pharmacokinetic parameters of cefpiramide, actisomide, troglitazone, procaterol, moxalactam and ciprofloxacin were scaled from animal data obtained from the literature . Three methods were used to generate plots for the prediction of clearance in man: dependence of clearance on body weight (simple allometric equation); dependence of the product of clearance and maximum life-span potential (MLP) on body weight; and dependence of the product of clearance and brain weight on body weight . Plasma concentrations of the drugs were predicted in man by use of A, B, alpha and beta obtained from animal data . The predicted plasma concentrations were then used to calculate CL, VdC and t1/2beta . The pharmacokinetic parameters predicted by use of both approaches were compared with measured values . The results indicate that simple allometry did not predict clearance satisfactorily for actisomide, troglitazone, procaterol and ciprofloxacin . Use of MLP or the product of clearance and brain weight improved the prediction of clearance for these four drugs . Except for troglitazone, VdC and t1/2beta predicted for man by use of the allometric approach were comparable with measured values for the drugs studied . CL, VdC and t1/2beta predicted by use of pharmacokinetic constants were comparable with values predicted by simple allometry . Thus, if simple allometry failed to predict clearance of a drug, so did the pharmacokinetic constant approach (except for actisomide) . The results of this study indicate that caution should be employed in interpreting plasma concentrations predicted for a drug in man by use of pharmacokinetic constants obtained in animals. Lett Appl Microbiol, 1999 Aug, 29(2), 113 - 7 Alterations in macromolecular composition and cell wall integrity by ciprofloxacin in Mycobacterium smegmatis; Verma I et al.; The present study has been undertaken to explore the biochemical mechanism of antimycobacterial action of a potent fluoroquinolone i.e . ciprofloxacin in Mycobacterium smegmatis . Cells grown in the presence of a subinhibitory concentration (IC50) of ciprofloxacin had a significantly lower content of all the major macromolecules i.e . DNA, RNA, proteins and lipids with maximum inhibition in DNA concentration as compared to control . Significant quantitative changes were also observed in the various chemical constituents of cell wall of ciprofloxacin grown cells . A decrease in the number of binding sites for a fluorescent probe L-anilinonapthalene-8-sulphonate (ANS) in ciprofloxacin grown cells suggested structural changes on the cell surface . Significant changes were also observed in the morphology of cells grown in the presence of ciprofloxacin by scanning electron microscopy (SEM) . Our results suggest that ciprofloxacin exerts its antimycobacterial activity by affecting the cell wall as well as various macromolecules, particular DNA, the vital component for cell survival and growth. J Vet Pharmacol Ther, 1999 Aug, 22(4), 239 - 46 Comparative study of the plasma pharmacokinetics and tissue concentrations of danofloxacin and enrofloxacin in broiler chickens; Knoll U et al.; The plasma pharmacokinetics of danofloxacin and enrofloxacin in broiler chickens was investigated following single intravenous (i.v.) or oral administration (p.o.) and the steady-state plasma and tissue concentrations of both drugs were investigated after continuous administration via the drinking water . The following dosages approved for the treatment of chickens were used: danofloxacin 5 mg/kg and enrofloxacin 10 mg/kg of body weight . Concentrations of danofloxacin and enrofloxacin including its metabolite ciprofloxacin were determined in plasma and eight tissues by specific and sensitive high performance liquid chromatography methods . Pharmacokinetic parameter values for both application routes calculated by noncompartmental methods were similar for danofloxacin compared to enrofloxacin with respect to elimination half-life (t1/2: approximately 6-7 h), mean residence time (MRT; 6-9 h) and mean absorption time (MAT; 1.44 vs . 1.20 h) . However, values were twofold higher for body clearance (ClB; 24 vs . 10 mL/min . kg) and volume of distribution at steady state (VdSS; 10 vs . 4 L/kg) . Maximum plasma concentration (Cmax) after oral administration was 0.5 and 1.9 micrograms/mL for danofloxacin and enrofloxacin, respectively, occurring at 1.5 h for both drugs . Bioavailability (F) was high: 99% for danofloxacin and 89% for enrofloxacin . Steady-state plasma concentrations (mean +/- SD) following administration via the drinking water were fourfold higher for enrofloxacin (0.52 +/- 0.16 microgram/mL) compared to danofloxacin (0.12 +/- 0.01 microgram/mL) . The steady-state AUC0-24 h values of 12.48 and 2.88 micrograms.h/mL, respectively, derived from these plasma concentrations are comparable with corresponding area under the plasma concentration-time curve (AUC) values after single oral administration . For both drugs, tissue concentrations markedly exceeded plasma concentrations, e.g . in the target lung, tissue concentrations of 0.31 +/- 0.07 microgram/g for danofloxacin and 0.88 +/- 0.24 microgram/g for enrofloxacin were detected . Taking into account the similar in vitro activity of danofloxacin and enrofloxacin against important pathogens in chickens, a higher therapeutic efficacy of water medication for enrofloxacin compared to danofloxacin can be expected when given at the approved dosages. Shock, 1999 Sep, 12(3), 235 - 41; discussion 242 Perturbed bioelectrical properties of the mouse cecum following hepatectomy and starvation: the role of bacterial adherence; Alverdy JC et al.; Previous work in our laboratory has demonstrated that bacterial adherence alone to the intestinal epithelium, as occurs following catabolic stress, significantly perturbs the normal electrophysiology of the cecal mucosa . The aim of this study was to further characterize these effects in the mouse cecum following hepatectomy and short-term starvation, and to define the role of bacterial adherence in this process . Groups of mice underwent a surgical hepatectomy and were either fed or starved during the postoperative period . Groups of controls underwent sham operations and were either fed or starved postoperatively . Electrophysiologic studies in Ussing chambers at 48 hours were performed . Bacterial adherence to the mucosa was assessed by culture and histologic staining . To determine the role of bacteria in the altered electrophysiologic response, ciprofloxacin decontamination studies were performed . Only mice subjected to both hepatectomy and starvation developed bacterial adherence of sufficient magnitude (>10(5) cfu/gm) to alter mucosal electrophysiology (short-circuit current and basal potential difference) . Ciprofloxacin decontamination completely abrogated this effect . Ion replacement studies suggested that active sodium transport was primarily responsible for the observed changes in mucosal electrophysiology . Bacterial-epithelial cell interactions may be responsible for altered mucosal ion transport observed following operative catabolic stress and short-term starvation. Clin Infect Dis, 1999 Aug, 29(2), 335 - 8 Enteroaggregative Escherichia coli as a cause of traveler's diarrhea: clinical response to ciprofloxacin; Glandt M et al.; The purpose of this study was to determine the role of enteroaggregative Escherichia coli (EAEC) in the development of traveler's diarrhea and the clinical response of patients with EAEC diarrhea following treatment with ciprofloxacin . Sixty-four travelers with diarrhea and no other recognized enteropathogen were enrolled in treatment studies in Jamaica and Mexico from July 1997 to July 1998 . EAEC was isolated from 29 travelers (45.3%) . There was a significant reduction in the duration of posttreatment diarrhea in the 16 patients treated with ciprofloxacin, as compared with that in the 13 patients who received placebo (mean of 35.3 versus 55.5 hours; P = .049) . There was a nonsignificant reduction in the mean number of unformed stools passed during the 72 hours after enrollment in the ciprofloxacin-treated group (5.6), as compared with that in the placebo group (7.5) (P = .128) . This study provides additional evidence that EAEC should be considered as a cause of antibiotic-responsive traveler's diarrhea. Alcohol Clin Exp Res, 1999 Aug, 23(8), 1403 - 8 Effects of ethanol on intestinal absorption of drugs: in situ studies with ciprofloxacin analogs in acute and chronic alcohol-fed rats; Ferrando R et al.; BACKGROUND: Previous work from our laboratory on the effect, in rats, of chronic ethanol intake on the intestinal absorption of ciprofloxacin analogs suggested an increased polarity of the lipoidal membrane constituents without effects on the aqueous environment . The aim of the present study was to investigate the influence of acute ethanol intake on the absorption of the same series of compounds . METHODS: The effects of in situ ethanol exposure on intestinal absorption were determined in rats fed either a standard liquid diet or a 5% (w/v) ethanol-containing liquid diet . Acute intestinal exposure to 5% (w/v) ethanol was performed in situ in each feeding group . The biophysical absorption model was used to establish correlations between the actual absorption rate constants, and the lipophilicity indexes, for each group of rats . RESULTS: Acute exposure to ethanol produces an increase only in the absorption of hydrophilic homologs in both control and chronic ethanol fed groups . This suggests the absence of homeoviscous adaptation of the intestinal membrane . The biophysical model used allows us to discriminate between the effects of acute and chronic ethanol treatment on the intestinal membrane . CONCLUSIONS: These results suggest that in contrast to previous reports chronic ethanol treatment increases membrane polarity and acute alcohol intake appears to modify membrane fluidity. Boll Chim Farm, 1999 Jun, 138(6), 239 - 42 Adsorption studies of ciprofloxacin: evaluation of magnesium trisilicate, kaolin and starch as alternatives for the management of ciprofloxacin poisoning; Ofoefule SI et al.; In vitro experiments were performed to investigated the extend of adsorption of ciprofloxacin to kaolin, magnesium trislilicate and to a starch obtained from the tubers of Tacca involucrata (Tacca starch) and to explore the effect of varying pH on this adsorption . Activated charcoal, a standard adsorbent and antidote in the management of poisoning due to a variety of chemical agents was employed as a comparing standard . The results of the study indicate that kaolin and magnesium trisilicate adsorbed ciprofloxacin effectively while the adsorption of the drug on the starch was relatively low . Adsorption was dependent upon the quantity of the adsorbed used . Kaolin or magnesium trisilicate could serve as an effective antidotal alternative to activated charcoal in the management of ciprofloxacin poisoning . Except in cases of poisoning due to ciprofloxacin, the concurrent administration of the drug with kaolin or magnesium trisilicate may be contraindicated . Tacca starch, however, may not really be recommended for the management of ciprofloxacin poisoning. Int J Antimicrob Agents, 1999 Aug, 12(3), 239 - 44 Enhanced susceptibility of pentylenetetrazole kindled mice to quinolone effects; De Sarro A et al.; The present study was designed to examine the ability of different quinolones to affect the seizure severity and the latency of development of chemical kindling produced by repeated treatment using a subconvulsant dose of pentylenetetrazole (PTZ) . A group of mice (kindled control) were treated subcutaneously (s.c.) with vehicle + PTZ (30 mg/kg, three times a week) for 6 consecutive weeks and the changes in excitability associated with the kindling state were observed over the following 2 h . A second group of mice were injected intraperitoneally (i.p.) with the following quinolone derivatives, ciprofloxacin (ciprox), pefloxacin (peflox), ofloxacin (oflox), cinoxacin (cinox), nalidixic acid (nalidixic), 1-cyclopropyl-6-amino-7-tetrahydroisoquinoline-8-methyl-4-oxo-1,4-dihydr oquinoline-3-carboxylic acid (M5) and 1-cyclopropyl-7-tetrahydro-isoquinoline-8-methyl-4-oxo-1,4-dihydroquinol ine-3-carboxylic acid (MH5) at a dose of 20 mg/kg 15 min before receiving a subconvulsant dose of PTZ (30 mg/kg, s.c.) . The results showed that pretreatment with some of the quinolones tested facilitated the development of kindling to PTZ-induced seizures . In particular, ciprox, peflox, oflox, M5 and MH5 derivatives variously increased the development of kindling to PTZ induced seizures, whilst cinox and nalidix did not significantly affect it . Additionally we determined whether the enhanced susceptibility of kindled mice only occurred after relatively short intervals following the last seizure or whether it was a more permanent phenomenon . For the study of the persistence of kindling, the animals were rechallenged with the kindling stimulus (PTZ 25 mg/kg, s.c.) 15 and 30 days after the last injection of the chronic treatment with PTZ (30 mg/kg, s.c.) and the behavioural changes in the kindled mice were compared with the control ones (chronically treated with vehicle) . The present data demonstrated that kindling produced long-lasting alterations, substantiating that epileptogenesis initiated by kindling renders the brain more susceptible to central nervous system (CNS) side effects of quinolones . An interaction between PTZ and quinolone derivatives which involves either an inhibition of gamma-aminobutyric acid (GABA) neurotransmission or/and an increase in the function of the excitatory amino acid (EAA) system is suggested. Am J Ophthalmol, 1999 Aug, 128(2), 236 - 7 Noninfectious crystalline keratopathy after postoperative subconjunctival 5-fluorouracil; Rothman RF et al.; PURPOSE: To describe a case of transient, noninfectious crystalline keratopathy after postoperative subconjunctival 5-fluorouracil . METHOD: Case report . Slit-lamp biomicroscopic examinations were performed during serial office examinations . RESULTS: A 69-year-old woman underwent an uncomplicated trabeculectomy with adjunctive sponge 5-fluorouracil application for 5 minutes in her left eye . Postoperative treatment included topical prednisolone acetate, ciprofloxacin, and scopolamine . She was initially examined with intrastromal corneal crystalline deposits 5 days after her first postoperative subconjunctival injection of 5-fluorouracil . The deposits completely disappeared 4 days later without addition to or change in treatment . CONCLUSION: Transient, noninfectious, crystalline, intrastromal corneal deposits may develop after adjunctive subconjunctival 5-fluorouracil administration. J Am Optom Assoc, 1999 Mar, 70(3), 193 - 7 Crack eye syndrome; Colatrella N et al.; BACKGROUND: Cocaine is an alkaloid prepared from the leaves of the Erythroxylon coca plant . It is widely recognized as one of the most dangerous illicit drugs in use today . The U.S . Substance Abuse and Mental Health Services Administration estimates that 23.5 million Americans have used cocaine at some time in their life . Corneal defects from crack cocaine were first described in 1989 and later named crack eye syndrome in 1993 . CASE REPORT: A 40-year-old man reported to the eye clinic reporting vigorous eye rubbing after repeated exposure to and use of crack cocaine . A corneal infiltrate with an overlying epithelial defect developed and the man was treated with ciprofloxacin, homatropine, and diclofenac . This case presents background information concerning the systemic and ocular manifestations of cocaine, as well as the clinical presentations of crack eye syndrome, with recommendations on treatment . CONCLUSIONS: A thorough social history should be elicited when patients who have unilateral or bilateral corneal defects of unknown origin are examined, or when treating persons with no other known risk factors for corneal disruption . Prompt recognition and treatment are the main factors in successful management of crack eye syndrome. South Med J, 1999 Aug, 92(8), 831 - 2 Infection of a knee prosthesis with Tsukamurella species; Larkin JA et al.; A 69-year-old woman with a history of multiple infections of a postoperative wound from a knee replacement was diagnosed with an infection with Tsukamurella sp . The infection was treated with a course of vancomycin and pipercillin/tazobactam, followed by a course of clarithromycin, ciprofloxacin, and ethambutol . The patient responded well . This represents the first report of a Tsukamurella infection of an artificial joint. Bone Marrow Transplant, 1999 Jul, 24(2), 197 - 9 Tularemia--an unusual cause of a solitary pulmonary nodule in the post-transplant setting; Naughton M et al.; We report a case of tularemia presenting as a solitary pulmonary nodule following syngeneic PBSC transplant . Seven months after undergoing a syngeneic PBSC transplant for AML, our patient presented with fever without localizing signs . Chest X-ray revealed a solitary pulmonary nodule . Culture of a CT guided needle aspiration revealed Francisella tularensis . The patient was successfully treated with ciprofloxacin . His fever resolved and clearance of the nodule was documented on a CT scan 2 months after diagnosis and initiation of treatment . To our knowledge, this is the only reported case of tularemia occurring in the post-transplant setting . The possible relationship between transplant-induced immune dysfunction and the occurrence of this rare infection is discussed. Br J Pharmacol, 1999 Aug, 127(7), 1728 - 34 Active intestinal elimination of ciprofloxacin in rats: modulation by different substrates; Dautrey S et al.; 1 . Two in vivo models, in the rat, were used to investigate, in the presence of different substrates, the overall and net intestinal elimination of ciprofloxacin: an open-intestinal perfusion model and an intestinal loop model respectively . 2 . In the presence of quinidine, verapamil and cyclosporin (substrates of the P-glycoprotein (P-gp)), plasma AUCs of ciprofloxacin were 1.5 - 2 fold increased, while biliary clearance (1.5 - 2 fold), intestinal overall and net clearances (2 - 4 fold and 1.5 - 8 fold respectively) decreased . The weak effect obtained with cyclosporin as compared to verapamil and especially quinidine, suggests, for ciprofloxacin, the existence of transport systems distinct from the P-gp, as the OCT1 transporter which could be inhibited by quinidine . 3 . With cephalexin and azlocillin, two beta-lactam antibiotics, plasma AUCs of ciprofloxacin increased and biliary and intestinal overall clearances decreased in a similar fashion (1.3 - 2 fold), suggesting the involvement of organic anion and/or cation transporters . 4 . In the presence of structural analogues, the effect was dependent on the compound administered: Sparfloxacin had no effect on intestinal clearance of ciprofloxacin . In contrast, with pefloxacin, overall intestinal clearance of ciprofloxacin was decreased and net intestinal clearance increased . 5 . The specificity of ciprofloxacin intestinal transport appears to be different from P-gp as outlined by the lack of competition with sparfloxacin, a P-gp substrate . Ciprofloxacin intestinal elimination seems to be mediated by organic anion and/or cation transporters and a mechanism sensitive to quinidine and verapamil. Scand J Infect Dis, 1999, 31(2), 131 - 3 African tick-bite fever imported into Norway: presentation of 8 cases; Jensenius M et al.; We report on 8 Norwegian travellers to Southern Africa with African tick-bite fever (ATBF), a recently described spotted fever group rickettsiosis . All patients had acute flu-like symptoms and developed I or multiple inoculation eschars . The patients were treated with either doxycycline or ciprofloxacin, and all recovered . The diagnosis of ATBF was confirmed by the detection of specific IgM antibodies to Rickettsia africae by microimmunofluoroscence in convalescent-phase serum samples. Pneumologie, 1999 Jul, 53(7), 360 - 3 {Aspiration pneumonia caused by vertebrae of a dove in a 39 year old patient with Down syndrome}; Muller R et al.; Undetected foreign body aspiration is a well-known problem not only in children and patients with predisposing conditions like mental retardation, seizures or brain tumours, but also in healthy subjects . The clinical signs are quite different . Haemoptysis, cough, recurrent or chronic penumonia and bronchitis may occur . These symptoms are often accompanied by fever, weight loss and night sweat . Atelectasis, respiratory distress or death have been described . We demonstrate the case of a 39-year old man with Down syndrome who was transferred to our hospital because of pneumonia in the left lower lobe that had been lasting for about two months . It had been resistant to several antibiotic regimens . Computerised tomography led to the suspicion of a bronchial carcinoma with poststenotic infiltration of the lower lobe . Fibreoptic bronchoscopy and biopsy confirmed the diagnosis of a foreign body in the distal part of the left main bronchus . After two weeks of treatment with ciprofloxacin regression of the acute inflammation occurred . During a second bronchoscopy we could extract the foreign body (a 1 x 1.7 cm vertebra of a dove) . It is concluded that undetected foreign body aspiration can occur in various clinical settings and fibreoptic bronchoscopy is a suitable approach providing an exact diagnosis. CLAO J, 1999 Jul, 25(3), 182 - 4 Penetration of topical ciprofloxacin by presoaked medicated soft contact lenses; Kalayci D et al.; PURPOSE: To assess the penetration of topical ciprofloxacin by a presoaked medicated disposable soft contact lens without topical drop administration . METHODS: Disposable soft contact lenses were presoaked in 0.3% topical ciprofloxacin (Ciloxan, Alcon Laboratories, Fort Worth,TX) for 10-12 hours . Presoaked lenses were placed on the eyes of patients with senile cataracts for 3 hours in group A, 5-6 hours in group B, and 8-12 hours in group C prior to their scheduled lens extraction surgery . Aqueous humor samples were drawn by paracentesis during the operation . Ciprofloxacin concentrations were determined by high pressure liquid chromatography-fluorescence detection . RESULTS: The mean ciprofloxacin concentration was 2.70 +/- 0.98 microg/mL in group A, 1.22 +/- 1.0 microg/mL in group B, and 0.5 +/- 0.2 microg/mL in group C . CONCLUSIONS: Penetration of topical ciprofloxacin is enhanced through a presoaked disposable soft contact lens, and at 3 hours therapeutic levels are obtained . Significant levels of ciprofloxacin are retained through 8-12 hours . This mode of treatment may increase patient compliance compared to frequent topical drop administration, and as a consequence, assure efficient treatment of keratitis, at least for the first 3 hours. Biopharm Drug Dispos, 1999 May, 20(4), 183 - 91 Kinetics of 4-fluoroquinolones permeation into saliva; Kozjek F et al.; Following a single oral administration of ciprofloxacin, norfloxacin, pefloxacin and ofloxacin preparations to healthy volunteers simultaneously collected, saliva and plasma 4-fluoroquinolone concentrations were assayed by HPLC . Pharmacokinetic properties were determined by ordinary least squares fitting of the two compartment pharmacokinetic model to the experimental data . A good correlation between plasma and saliva data has been demonstrated . The saliva to venous plasma drug concentration ratio S/P appeared to be time-dependent in the case of norfloxacin and pefloxacin . It was demonstrated that S/P is a function of the quotient of the rate of absorption and venous plasma drug concentration . The calculated S/P ratios with the influence of absorption eliminated, (S/P)(corr) are: ciprofloxacin 0.53+/-0.02, norfloxacin 0.34+/-0.04, ofloxacin 0 . 43+/-0.02 and pefloxacin 0.39+/-0.02 (mean+/-S.E.) . These values are apparently independent of log D thus making it impossible to predict S/P on the basis of partition principles . The corresponding (S/P)(dif) ratios were calculated on the basis of the assumption that an equilibrium is established across the blood-saliva barrier, which is permeable only for nonionized and nonprotein bound drug fraction . Comparing (S/P)(corr) with the calculated (S/P)(dif) ratios it is evident that 4-fluoroquinolone permeation in saliva cannot be described by passive diffusion based on pH-partition theory . FEMS Microbiol Lett, 1999 Aug 1, 177(1), 131 - 5 Regioselective transformation of ciprofloxacin to N-acetylciprofloxacin by the fungus Mucor ramannianus; Parshikov IA et al.; A strain of the saprobic fungus Mucor ramannianus, isolated from a forest, was used to demonstrate the potential for ciprofloxacin biotransformation by zygomycetes in the environment . The fungus carried out the regioselective N-acetylation of ciprofloxacin to a single product, which was purified from culture extracts by high-performance liquid chromatography . The metabolite was identified by mass and nuclear magnetic resonance spectrometry as 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-acetyl-1-piperazinyl)-3- quinolinecarboxylic acid. Analyst, 1998 Dec, 123(12), 2789 - 96 Extension of multi-residue methodology to include the determination of quinolones in food; Rose MD et al.; The multi-residue procedure for basic drugs described elsewhere by this laboratory has been evaluated for quinolone and fluoroquinolone antibiotics . The fluoroquinolones are a relatively new class of drug and an increasing number of licensed products containing these compounds are becoming available for use in animal husbandry . This, along with the possibility of the development of antibiotic resistant human pathogens, make it an important class of drug for which methodology is required for the monitoring of residues in food . Validation data are presented for a range of compounds including the quinolones; oxolinic acid and nalidixic acid, and the fluoroquinolones; flumequine, ciprofloxacin, danofloxacin, enoxacin, enrofloxacin, lomefloxacin, marbofloxacin, norfloxacin, ofloxacin and sarafloxacin . Foods for which the method was validated included poultry muscle (chicken and turkey), egg, chicken liver, honey, cattle muscle and pig muscle . This application of the multi-residue procedure further demonstrates the importance and wide-ranging usefulness of the technique. Analyst, 1998 Dec, 123(12), 2729 - 32 Determination of ciprofloxacin and enrofloxacin in edible animal tissues by terbium-sensitized luminescence; Hernandez-Arteseros JA et al.; A terbium-sensitized luminescence method is described for the determination of the sum of residues of enrofloxacin and its major metabolite ciprofloxacin in edible animal tissues . Several parameters affecting both detection and extraction were studied . Analytes were extracted from spiked samples of chicken and trout tissues with pH 7.4 buffer-dichloromethane . The organic extract was evaporated and the residue dissolved in aqueous nitric acid and defatted with hexane . Determination was carried out directly in the aqueous phase (in a micellar medium) . The calibration curves were linear up to 75 micrograms l-1 . The detection limit was 3.5 micrograms kg-1 (for a 5 g sample) and the repeatability was 7.0% (n = 7) . The sensitivity was similar for both quinolones and therefore calibration can be carried out with either ciprofloxacin or enrofloxacin . In any case, the differences were < 10%. Am J Otol, 1999 Jul, 20(4), 416 - 20 The effect of topical ciprofloxacin on postoperative otorrhea after tympanostomy tube insertion; Zipfel TE et al.; OBJECTIVE: This study aimed to evaluate the effectiveness of prophylactic ciprofloxacin drops in decreasing the incidence of otorrhea after tympanostomy tube insertion . STUDY DESIGN: The study design was a single-blind, randomized clinical trial . SETTING: The study was conducted at a tertiary care referral center . PATIENTS: One hundred fifty-four patients aged 6 months to 14 years undergoing tympanostomy tube insertion participated . INTERVENTION: For each subject, one ear was randomly assigned to receive topical ciprofloxacin, placed in the middle and external ear after surgery, while the contralateral ear served as a control . MAIN OUTCOME MEASURE: Posttympanostomy otorrhea occurring during the period from 24 hours after surgery until 2 weeks after surgery was measured . RESULTS: Topical ciprofloxacin application after tympanostomy tube insertion was associated with a significantly lower incidence of early posttympanostomy otorrhea . The rates of otorrhea for control and treatment ears were 9.1% and 3.9%, respectively (p = 0.029) . CONCLUSIONS: The topical administration of a single dose of ciprofloxacin solution after surgery is an effective treatment for the prevention of early posttympanostomy otorrhea. Antimicrob Agents Chemother, 1999 Aug, 43(8), 2056 - 8 Penetration of ciprofloxacin into the interstitial space of inflamed foot lesions in non-insulin-dependent diabetes mellitus patients; Muller M et al.; Interstitial ciprofloxacin concentrations were measured by microdialysis in inflamed foot lesions of non-insulin-dependent diabetes mellitus patients following intravenous administration of 0 . 2 g of ciprofloxacin . Interstitial ciprofloxacin concentrations were significantly lower than corresponding serum concentrations . There was no significant difference in the penetration of ciprofloxacin into inflamed and unaffected tissue (area under the concentration-time curve(infection)/area under the concentration-time curve(unaffected tissue) = 0.99 +/- 0.15 {mean +/- standard error}, n = 6) . Thus, inflammation appears to have little or no effect on the penetration of ciprofloxacin into tissue. Biomed Chromatogr, 1999 Aug, 13(5), 350 - 3 Simultaneous determination of enrofloxacin and its primary metabolite, ciprofloxacin, in plasma by HPLC with fluorescence detection; Garcia MA et al.; A simple and sensitive HPLC method has been developed for the simultaneous determination of enrofloxacin (ENR) and ciprofloxacin (CIP) in plasma . Plasma sample preparation was carried out by adding phosphate buffer (pH 7.4, 0.1 M), followed by extraction with trichloromethane . ENR, CIP and the internal standard, sarafloxacin (SAR), were separated on a reversed-phase column, and eluted with aqueous acetonitrile (80:20) . The fluorescence of the column effluent was monitorized at lambda(ex) 338 and lambda(em) 425 nm . The retention times were 2.28, 3.30 and 4.40 min for CIP, ENR and SAR, respectively . The detection limit for the two compounds was 10 ng/mL . Standard curves were linearly related to concentration in the range from 1 to 1500 ng/mL . The recovery was 93% for ENR and 75% for CIP . Biomed Chromatogr, 1999 Jun, 13(4), 279 - 85 Determination of fluoroquinolone residues in animal tissues by liquid chromatography; Posyniak A et al.; A simple liquid chromatographic (LC) method was developed for the determination of fluoroquinolones (ciprofloxacin, difloxacin, enrofloxacin and sarafloxacin) in animal tissues . Isolation of fluoroquinolones from biological matrices was performed with 5% trichloroacetic acid-acetonitrile (7:3) solution . For clean-up, solid-phase extraction with an SDBI (styrene-divinylobenzene) cartridge was used . LC analyses were performed with analytical column (LiChrospher 100 RP-8 5 microns) and mobile phase (0.025 M o-phosphoric acid-acetonitrile 70:30, v/v) in ion-pair mode . The whole procedure was validated in intra- and inter-assay reproducibility and accuracy determination by simultaneously assaying of muscle, liver and kidney samples supplemented with fluoroquinolones at the level of 30 and 60 ng/g, respectively . The statistical evaluation demonstrates high absolute recovery (> 80%) and low coefficient of variation (< 10%) for all analysed samples . The detection limits for fluoroquinolones were 5 ng/g in muscle, liver and kidney samples. Hum Exp Toxicol, 1999 Jun, 18(6), 392 - 9 The comparative arthropathy of fluoroquinolones in dogs; Takizawa T et al.; 1 . Fluoroquinolone antibiotics are generally only prescribed to paediatric patients on compassionate grounds . This is because they are known to cause lesions in the cartilage of the major diarthroidal joints in immature experimental animals . As dogs are considered to be the most sensitive species, a series of studies was performed to compare the potential for grepafloxacin (a new fluoroquinolone) to cause arthropathy to that of ofloxacin and ciprofloxacin in juvenile (3 month old) beagles . 2 . Grepafloxacin was administered once daily to male juvenile dogs at dosages of up to 100 mg/kg/day (intravenously), 60 mg/kg/day (orally) or 30 mg/kg/day (subcutaneously) for 1 week . Blister formation was observed on the surface of the joints in one of the three animals treated with grepafloxacin intravenously at 100 mg/kg/day . No abnormalities were observed at lower dosages or when grepafloxacin was administered orally or subcutaneously, regardless of dose . In animals treated with ofloxacin or ciprofloxacin at dosages of 10-30 mg/kg/day, blister formation or erosion was observed on the surface of joints regardless of dose or route of administration . 3 . Histopathological examination of the joint surfaces of affected animals revealed the loss of cartilaginous matrix and chondrocytes, cavitation within the intermediate zone of cartilage accompanied by cartilage fibrillation or chondrocyte clustering, or loss of the surface layer which covers the cavitation (or loss of outer wall of the cavity) . These findings were not present in the absence of grossly observed lesions . 4 . Absorption following oral administration of grepafloxacin was low . Examination of plasma concentrations of drug following intravenous administration showed that joint toxicity was seen with ofloxacin and ciprofloxacin at maximum concentrations as low as 3.80 and 4.24 mg/l, respectively, while plasma levels of grepafloxacin of up to 11.95 mg/l failed to cause such lesions . When the concentration of grepafloxacin was 18.69 mg/l a single joint lesion was seen . Following subcutaneous administration of grepafloxacin, systemic exposure (area under the curve) of approximately 1.5 times that seen in man was not associated with joint lesions . However, lesions were noted for ofloxacin and ciprofloxacin treated animals at exposures equal to or below those seen in man . Therefore grepafloxacin appeared to have a relatively low potential for joint toxicity; this was not due to lack of penetration into the synovial fluid. J Pharm Pharmacol, 1999 May, 51(5), 609 - 16 Distribution of ciprofloxacin into the central nervous system in rats with acute renal or hepatic failure; Naora K et al.; Pharmacokinetic changes of various drugs have been reported in renal or hepatic failure . The present study employed ciprofloxacin, a quinolone antibiotic having neurotoxic side effects, to assess the influence of these diseases on distribution of ciprofloxacin into the central nervous system (CNS) . After intravenous dosing of ciprofloxacin (10-30 mg kg(-1)), ciprofloxacin levels in plasma and brain were measured in normal rats (Wistar, male, 10-week-old) and those with acute renal and hepatic injuries which were induced by uranyl nitrate and carbon tetrachloride (CCl4), respectively . In the uranyl nitrate-treated rats, the plasma elimination half-life of ciprofloxacin was prolonged and the total body clearance was reduced when compared with those in the normal rats . Similar but smaller changes were observed in the CCl4-treated group . Brain levels of ciprofloxacin were significantly increased by both uranyl nitrate and CCl4 treatments . A proportional correlation between serum unbound levels and brain levels of ciprofloxacin was observed in the normal group . However, brain-to-serum unbound concentration ratios of ciprofloxacin were reduced in the rats with renal or hepatic failure . These results suggest that renal failure as well as hepatic failure retards elimination of ciprofloxacin from the blood, leading to elevation of the CNS level, and also that ciprofloxacin distribution in the brain is reduced in these disease states. Intensive Care Med, 1999 May, 25(5), 486 - 91 Pharmacokinetics of cefpirome during the posttraumatic systemic inflammatory response syndrome; Jacolot A et al.; OBJECTIVE: To determine the pharmacokinetic parameters of cefpirome, a new so-called fourth-generation cephalosporin, in previously healthy trauma patients with posttraumatic systemic inflammatory response syndrome (SIRS) and to compare them to parameters obtained in matched, healthy volunteers . DESIGN: A prospective study . SETTING: 12-bed surgical intensive care unit in a university hospital . PATIENTS: 9 severe {Injury Severity Score, median (range) 29 (16-50)} trauma patients on mechanical ventilation with proven or suspected cefpirome-susceptible nosocomial infection, with no renal or hepatic failure, and healthy volunteers matched for age (+/- 5 years), sex, and body surface area (+/- 10%) were enrolled . All were men . INTERVENTIONS: Cefpirome (2 g twice daily) was continuously infused over a 0.5 h period alone or concomitantly with ciprofloxacin (400 mg over 1 h, twice daily) . MEASUREMENTS AND MAIN RESULTS: Antibiotic concentrations in plasma were measured by high-performance liquid chromatography; their pharmacokinetic parameters were evaluated at 12 time points after the first drug administration using a noncompartmental model . Cefpirome pharmacokinetic parameters for the two groups were similar despite a wider variation for trauma patients . Specifically, the median (range) time during which the cefpirome concentration in plasma remained over 4 mg/l (corresponding to the French lower cutoff determining cefpirome susceptibility) was 9.5 (7- > 12) and 9 (8-12) h for trauma patients and healthy volunteers, respectively . In the group of five patients receiving combined antibiotic therapy, the interindividual variability of pharmacokinetics was wider for ciprofloxacin than for cefpirome . CONCLUSION: No major pharmacokinetic modification was noted when cefpirome was given to trauma patients with posttraumatic SIRS without significant organ failure, indicating that no dosage adjustment seems required in this population . However, larger studies including determination of antibiotic levels in tissues are warranted to confirm these results. Ophthalmic Surg Lasers, 1999 Jun, 30(6), 465 - 8 Penetration of ofloxacin and ciprofloxacin in aqueous humor after topical administration; Cekic O et al.; BACKGROUND AND OBJECTIVE: To compare the aqueous humor levels of 0.3% ofloxacin and 0.3% ciprofloxacin containing eyedrops in patients with healthy cornea . PATIENTS AND METHODS: Fifty patients with cataract were randomly assigned to have 0.3% ofloxacin containing eyedrop (25 patients) or 0.3% ciprofloxacin containing eyedrop (25 patients) . Both drugs were repetitively instilled to each patient for 6 hours before the surgery . Aqueous samples were collected after penetrating the anterior chamber during cataract extraction and assayed by high-performance liquid chromatography method . RESULTS: The aqueous humor level of ofloxacin (1.43 +/- 0.26 microg/ml, mean +/- SEM) was significantly higher than that of ciprofloxacin (0.35 +/- 0.07 microg/ml) following the topical application (P < .0002) . CONCLUSION: Aqueous humor penetration of topical ofloxacin is about 4 times higher than that of topical ciprofloxacin when the drugs are applied as described above. Cancer, 1999 Jul 1, 86(1), 126 - 34 Outpatient treatment of fever and neutropenia for low risk pediatric cancer patients; Mullen CA et al.; BACKGROUND: Fever and neutropenia (F&N) is a common complication of cancer chemotherapy . It is conveniently managed by hospitalization and empiric administration of parenteral antibiotics . This study attempted to determine whether pediatric cancer patients with F&N identified as low risk for morbidity and mortality by clinical criteria at the time of presentation could be treated safely as outpatients . METHODS: Seventy-three episodes of F&N in 41 patients were studied prospectively over 2 years . Eligibility criteria included age > or =2 years, reliable caretakers, and residence within 1 hour of the hospital . Exclusion criteria included hemodynamic instability, dehydration, severe mucositis, pneumonia, leukemia/lymphoma induction therapy, bone marrow transplantation, or other serious comorbidity . Patients were evaluated, received a single dose of intravenous ceftazidime, and were observed for 3-16 hours . They were randomized to receive either oral ciprofloxacin or intravenous ceftazidime as outpatients . Patients were seen daily until they had been afebrile for at least 48 hours and had a rising absolute phagocyte count of >500 cells/microL . RESULTS: Sixty-three of 73 episodes (86%) were successfully managed on an outpatient basis . For 31 of 33 episodes in the ceftazidime arm, the patients remained outpatients, compared with 32 of 40 in the ciprofloxacin arm; this difference was not statistically significant . On average, patients remained febrile for 2.7 days and were treated for 4.7 days . Seventy-seven percent of episodes required no modification of initial antibiotic therapy . Of the 10 patients who were hospitalized, 4 had prolonged fever and 3 had emesis . Protracted neutropenia was associated with the need for hospitalization . There were no deaths, intensive care unit transfers, or serious complications . CONCLUSIONS: Carefully selected low risk children with fever and neutropenia can be treated safely as outpatients . Close daily medical scrutiny is required. Antimicrob Agents Chemother, 1999 Jul, 43(7), 1729 - 36 Effects of novel 6-desfluoroquinolones and classic quinolones on pentylenetetrazole-induced seizures in mice; De Sarro A et al.; There have been several reports that convulsions, although rare, occur in patients who receive fluoroquinolones . In this study, the proconvulsant effects exhibited by a novel series of 6-desfluoroquinolones and some classic quinolones on pentylenetetrazole (PTZ)-induced seizures in mice were evaluated and compared . Animals were intraperitoneally injected with vehicle or quinolone derivatives (5 to 100 microg/g of body weight) 30 min before the subcutaneous (s.c.) administration of PTZ (40 microg/g) . In each experiment, mice were then observed for 1 h to monitor for the incidence and onset of clonic seizures . The order of proconvulsant activity in our epileptic model was MF5184 > MF5187 > pefloxacin > MF5189 > ofloxacin > ciprofloxacin > MF5140 > MF5181 > MF5137 > rufloxacin > MF5143 > MF5158 > MF5191 > MF5128 > MF5138 > cinoxacin > MF5142 > norfloxacin > nalidixic acid . The relationship between the chemical structure and the proconvulsant activity of 6-desfluoroquinolone derivatives was studied . We observed that, in terms of toxicity to the central nervous system (CNS), besides the heterocyclic side chain (moiety) at the C-7 position, the C-6 substituent also appears to play an important role . In particular, a hydrogen at the C-6 position seemed to be responsible for major neurotoxic activity in comparison to an amino group located in the same position . The relationship between lipophilicity and proconvulsant activity was also investigated . We did not find any clear relationship between a higher level of lipophilicity and major proconvulsant properties . Although the principal mechanism by which quinolones induce potentiation of the proconvulsant effects of PTZ cannot be easily determined, it is possible that the convulsions are caused by drug interactions, because both PTZ and quinolones are believed to increase excitation of the CNS by inhibition of gamma-aminobutyric acid binding to receptors. Pol J Pharmacol, 1999 Jan-Feb, 51(1), 71 - 8 Influence of fluoroquinolones on the central action of ethanol; Strzelec JS et al.; The influence of ciprofloxacin, ofloxacin and pefloxacin on acute toxicity of ethanol, ethanol-induced hypothermia, ethanol sleeping time was investigated in mice . Moreover, the combined effect of fluoroquinolones and ethanol on spontaneous locomotor activity, motor coordination in mice and ethanol abstinence syndrome in rats was examined . The fluoroquinolones (20 and 80 mg/kg) were injected intraperitoneally . The drugs were given in single or repeated doses for 7 days . In acute experiments, drugs were given 30 min before ethanol administration . In chronic experiments, the last dose of fluoroquinolones was given 18 h prior to ethanol injection . It has been shown that the fluoroquinolones decrease acute toxicity of ethanol, antagonize its hypothermic effect, decrease ethanol inhibitory effect on motor coordination in mice, and increase ethanol-induced hypermotility in mice and audiogenic seizure response in rats during alcohol abstinence syndrome . Ciprofloxacin and ofloxacin administered repeatedly increase the influence of ethanol on duration of ethanol-induced sleep . The influence of fluoroquinolones on ethanol central action depends on the drug used, its dose and route of administration. Transplantation, 1999 Jun 15, 67(11), 1495 - 6 Mycobacterium marinum infection in a renal transplant recipient; Farooqui MA et al.; BACKGROUND: Infections with atypical mycobacteria occur more frequently in patients with solid organ transplants than in the normal host . METHODS: We report a case of cutaneous Mycobacterium marinum infection in a renal transplant recipient . The patient presented with nodules on the forearm after returning from a fishing trip and was treated for cellulitis without success . RESULTS: Cultures of a biopsy of the lesion grew M . marinum . The patient was treated with ethambutol and ciprofloxacin with a good response; however, 9 months of treatment were required for complete resolution . CONCLUSION: Immunosuppressive therapy for renal transplantation increases susceptibility to a variety of opportunistic infections . A patient who presents with nodules on the extremities should be questioned regarding contact with fish, aquatic environments, or fish tank water, in which case infection with M . marinum should be considered . The diagnosis and treatment of this infection in transplant recipients is discussed. J Periodontal Res, 1999 Apr, 34(3), 145 - 53 Phenytoin metabolism to 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH) in man, cat and rat in vitro and in vivo, and susceptibility to phenytoin-induced gingival overgrowth; Kamali F et al.; Interspecies differences in phenytoin (PHT) metabolism to 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH) were examined in human, cat and rat hepatic microsomes in vitro . Rat liver microsomes were 25 and 650 times more efficient at the conversion of PHT to HPPH than human and cat liver microsomes, respectively . Sulphaphenazole (83%) and tolbutamide (TOL) (64%) were the most potent inhibitors of HPPH formation in human liver microsomes, while ciprofloxacin (27%), enoxacin (27%) and TOL (26%) produced the greatest inhibition in cat liver microsomes . TOL was tested for its effect on HPPH formation and gingival overgrowth in cats in vivo . Eight cats received PHT sodium (4 mg/kg/d) and another 8 cats received PHT sodium together with TOL (20 mg/kg/d) for 10 wk . Six cats (75%) in the PHT group and 4 cats (50%) in the PHT & TOL group developed significant gingival overgrowth by the end of the study . However, the extent and incidence of the overgrowth were similar in the 2 groups . There were no significant differences in mean AUC 0-10 weeks for plasma PHT (552.90 +/- 29.6 micrograms.d/mL {PHT alone} vs . 582.41 +/- 24.49 micrograms.d/mL {PHT & TOL}) and unconjugated HPPH (1016.4 +/- 295.5 ng.d/mL {PHT alone} vs . 1174.5 +/- 397.2 ng.d/mL {PHT & TOL}) concentrations between the 2 groups of cats . Neither PHT nor HPPH were detectable in the plasma of 8 rats which received PHT (4 mg/kg/d) over a 10-wk period . The rats showed no sign of gingival inflammation (mean gingival index = 0) or gingival overgrowth (mean gingival overgrowth index = 0) . Thirty-six adult epileptic patients on chronic PHT therapy were examined; 17 (47%) of the patients demonstrated clinically significant overgrowth . The mean steady-state plasma PHT concentration was comparable to, and the mean plasma unconjugated HPPH concentration 5-fold greater than, that observed in the cats . The results suggest that the rapid metabolism and elimination of PHT and HPPH in the rat may enable it to become more resistant towards developing gingival overgrowth, compared to the cat and man. J Antimicrob Chemother, 1999 May, 43(5), 741 - 3 Prevention of febrile leucopenia after chemotherapy in high-risk breast cancer patients: no significant difference between granulocyte-colony stimulating growth factor or ciprofloxacin plus amphotericin B; Schroder CP et al.; In a prospective randomized trial, 40 stage IV breast cancer patients undergoing intermediate high-dose chemotherapy (cyclophosphamide, 5-fluorouracil plus epirubicin or methotrexate), received either recombinant human G-CSF (rhG-CSF, group I) or ciprofloxacin and amphotericin B (CAB, group II) for prevention of febrile leucopenia (FL) . In group I, seven of 18 patients developed FL (after 10/108 courses); in group II, seven of 22 patients (7/98 courses) (P = NS) . Median hospitalization duration and costs were not different . RhG-CSF was 6.6 times more expensive per course than CAB . In conclusion, prophylactic CAB has similar efficacy to rhG-CSF in this setting, and is more cost-effective. Eur J Pharm Sci, 1999 Jul, 8(3), 203 - 9 Distribution of ciprofloxacin in the isolated rat lung in the presence and absence of tissue oedema; Reinoso RF et al.; A series of experiments with the isolated perfused rat lung was carried out to study the distribution of ciprofloxacin in this tissue under different experimental conditions; the influence of drug administration rate and the presence of oedema were evaluated by comparison of the statistical moment and distribution coefficient values as well as the unit disposition function (UDF) profiles in the tissue . The polyexponential character of the outflow perfusate curves indicates a distribution behaviour which does not correspond to the 'well stirred model' but rather to the existence of some type of diffusion barriers and/or tissue binding . The presence of oedema in the tissue, induced by insufficient oxygenation of perfusate, significantly increases the distribution coefficient of ciprofloxacin and leads to relevant modifications in the unit disposition function (UDF) of the isolated lung, while administration rate does not significantly affect the kinetic behaviour of the drug in this tissue. BJU Int, 1999 Jun, 83(9), 1055 - 9 The role of vitamin A in preventing renal scarring secondary to pyelonephritis; Kavukcu S et al.; OBJECTIVE: To evaluate the efficiency of exogenously administered vitamin A in preventing renal scarring caused by experimental pyelonephritis in rats . MATERIALS AND METHODS: Forty Wistar rats were injected with 0.1 mL of solution containing Escherichia coli (1010 /mL) into both renal medullae . Five equal groups were then formed: group 1 was treated only with ciprofloxacin (30 mg/kg per day, twice daily, intraperitoneally) for 5 days, starting 3 days after bacterial inoculation; in group 2, 60 kIU of vitamin A was injected intramuscularly with the bacterial inoculation; in group 3, 60 kIU of vitamin A was injected similarly, but 3 days after bacterial inoculation; in group 4, 60 kIU of vitamin A was given orally with the bacterial inoculation; and group 5 was treated with ciprofloxacin for 5 days and vitamin A intramuscularly from the third day after bacterial inoculation . All the rats were killed 6 weeks after bacterial injection; blood samples were obtained to determine serum vitamin A and beta-carotene levels, and both kidneys were examined pathologically for scarring, graded as 0 (none), 1 (mild), 2 (moderate) and 3 (severe) . RESULTS: Serum vitamin A levels were higher in the rats given vitamin A (group 2-5) than in group 1, being highest in group 4, although only this group had significantly higher levels of vitamin A than group 1 (P<0.05) . Histopathologically, the fibrosis was mildest in groups 2 and 4 (two of 16 kidneys grade 1), whereas it was most severe in group 1 (all 16 grade 2-3) . Fibrosis was significantly less in groups 2-5 than in group 1 (P<0.05) . There was a significant negative correlation between vitamin A levels and the sum of the fibrosis, inflammation and tubular atrophy scores of all rats (r=-0.391, P<0.02) . beta-carotene levels were unrelated to renal scarring . CONCLUSION: The administration of vitamin A could have a role in preventing renal scar formation from pyelonephritis induced experimentally in rats. J AOAC Int, 1999 May-Jun, 82(3), 607 - 13 Determination of four fluoroquinolones in milk by on-line immunoaffinity capture coupled with reversed-phase liquid chromatography; Holtzapple CK et al.; An automated, on-line immunoaffinity extraction method was developed for the analysis of 4 fluoroquinolones in milk: ciprofloxacin, difloxacin, enrofloxacin, and sarafloxacin . This method involves analyte extraction using an immunoaffinity capture column containing anti-fluoroquinolone antibodies coupled on-line with reversed-phase column chromatography . Liquid chromatographic analyses were performed by isocratic elution using a mobile phase of 2% acetic acid-acetonitrile (85 + 15) and an Inertsil phenyl column with fluorescence detection at excitation and emission wavelengths of 278 and 444 nm, respectively . No significant interferences from the sample matrix were observed, indicating good selectivity with the immunoaffinity column . Recoveries from fortified raw milk samples (5-50 ppb of each fluoroquinolone) ranged from 72 to 90%, with standard deviations of < or = 8%. Indian J Exp Biol, 1999 Jan, 37(1), 86 - 8 Effect of ciprofloxacin on steady state pharmacokinetics of phenytoin in rabbits; Islam AF et al.; Present study was undertaken to determine if an interaction exists during co-administration of ciprofloxacin with phenytoin . Eight healthy male rabbits received oral phenytoin, 40 mg/kg, od, for 7 days . On day 7, phenytoin blood sampling was done at times 0, 0.1, 1, 2, 3, 4, 5, 6, 8 and 24 hr . From day 8 to 14, phenytoin was co-administered with oral ciprofloxacin, 70 mg/kg, od . On day 14, blood samples were collected as previously described . Pharmacokinetic analysis revealed significant decrease in steady state maximum concentration (Cmax), through concentration (Cmin), elimination half life (t 1/2 e) and the area under plasma time concentration curve (AUC0-24) of phenytoin when co-administered with ciprofloxacin . It warrants close monitoring of levels when these two agents are given simultaneously. J Chromatogr B Biomed Sci Appl, 1999 Apr 16, 726(1-2), 175 - 84 Simultaneous determination of enrofloxacin and ciprofloxacin in animal biological fluids by high-performance liquid chromatography . Application in pharmacokinetic studies in pig and rabbit; Manceau J et al.; A simple and rapid high-performance liquid chromatographic method for the simultaneous determination of enrofloxacin and ciprofloxacin has been developed in pig and rabbit samples . Solid-phase extraction was applied from samples on a C18 cartridge using a mixture of methanol-hydrochloric acid (98:2, v/v) . Analytical separation was performed on a C18 column with UV detection at 277 nm under gradient conditions . The mobile phase was a mixture of orthophosphoric acidtriethylamine-acetonitrile . The method has been validated for both molecules in pig and rabbit plasma and adapted for rabbit tissue-cage fluid (TCF) . The assay is specific and reproducible within the both drugs and mean recoveries for ciprofloxacin and enrofloxacin, respectively, were 92+/-6% and 90+/-5% for pig plasma over the range used . Mean recoveries for enrofloxacin were 108+/-9% and 102+/-7% for rabbit plasma and TCF, respectively, over the range used . The suitability of the assay for pharmacokinetic studies was determined by measuring enrofloxacin and ciprofloxacin concentrations either in pig plasma after administration of a single intravenous 5 mg/kg dose of enrofloxacin or in rabbit plasma and TCF during a 24 h infusion of enrofloxacin at a rate of 1.25 mg/kg per hour. J Chromatogr A, 1999 Apr 23, 840(1), 11 - 20 Preconcentration of quinolones by dialysis on-line coupled to high-performance liquid chromatography; Zupancic T et al.; The parameters influencing dialytic separation of ciprofloxacin (CF) fluoroquinolone were investigated . Dialysis with a porous cellulose acetate membrane was on-line coupled with HPLC and the analysis of dialy