Urol Int, 2002, 69(1), 33 - 5 Brucellar orchitis in Innerwest Anatolia Region of Turkey . A report of 12 cases; Kadikoylu G et al.; Brucellosis, which affects the genitourinary system in rate of 2-20%, is a multiorgan infectious disease . Twelve patients were diagnosed as having brucellar orchitis serologically, clinically and ultrasonographically . In 2 patients, Brucella melitensis was isolated in blood cultures . All the patients were working in cattle dealing . They were treated with 600 mg/day rifampicin plus 200 mg/day doxycycline for 6 weeks and followed up during 1 year . They recovered clinically within 3 weeks . Although they did not have any symptoms or findings, in 4 patients, serological titers did not return to normal after 6 weeks . In 2 of these patients, relapse was seen in the 6th and 8th months, respectively . These 2 patients recovered with 1 g/day ciprofloxacin plus 2 g/day tetracycline for 6 weeks . Relapse did not occur again . Conclusively, brucellosis must be considered as a cause of orchitis in especially endemic regions where cattle dealing is widespread . The patients must be followed for relapse during at least 1 year . J Control Release, 2002 Jul 18, 82(1), 83 - 93 Characterization of crosslinked high amylose starch matrix implants . 1 . In vitro release of ciprofloxacin; Desevaux C et al.; The objective of this study was to characterize in vitro the potential of crosslinked high amylose starch (CLHAS) as an implant matrix for the delivery of ciprofloxacin (CFX) . Direct compression of dry blends of four different matrices: control CLHAS; CLHAS with 1% hydrogenated vegetable oil (HVO); and CLHAS with 10 or 20% hydroxypropylmethylcellulose (HPMC), each of them with three CFX loadings (2.5, 5.0 and 7.5%) was performed to prepare twelve implant formulations . All CLHAS implants were used for 24-h dissolution tests to evaluate swelling, erosion, water uptake and CFX release . Additionally, 1%-HVO- CLHAS implants were used for an extended dissolution test . The presence of HPMC in the matrix increased CFX release rate, swelling, erosion and water uptake in a concentration-dependent manner whereas HVO had no effect . With increasing drug loading, a decrease of cumulative CFX percent release was observed in both 24-h and extended dissolution tests . Of the different formulations tested, CLHAS implants with 1% HVO and 7.5% CFX provided the longest period of drug delivery without any initial burst effect . J Pharm Biomed Anal, 2002 Jul 31, 29(5), 859 - 64 Sensitive spectrophotometric methods for the determination of amoxycillin, ciprofloxacin and piroxicam in pure and pharmaceutical formulations; Nagaralli BS et al.; Two simple, sensitive and accurate spectrophotometric methods have been proposed for the determination of amoxycillin (AMX), ciprofloxacin (CPF) and piroxicam (PIR) in pure and pharmaceutical preparations . The methods are based on the measurement of absorbances of tris(o-phenanthroline) iron(II) {method A} and tris (bipyridyl) iron(II) {method B} complexes at 510 and at 522 nm, respectively . Reaction conditions have been optimized to obtain coloured complexes of higher sensitivity and longer stability . The absorbances were found to increase linearly with increase in concentrations of AMX, CPF and PIR which were corroborated by correlation coefficient values . The complexes obeyed Beer's law over the concentration range of 0.06-5.2, 0.04-7.2 and 0.2-6.5 microg ml(-1) for AMX, CPF and PIR, respectively, in method A, and of 0.05-8.5, 0.05-9.0 and 0.05-6.5 microg ml(-1) for AMX, CPF and PIR, respectively, in method B . The developed methods have been successfully applied for the determination of AMX, CPF and PIR in bulk drugs and pharmaceutical formulations . The common excipients and additives did not interfere in their determinations . The results obtained by the proposed methods have been statistically compared by means of Student t-test and by the variance ratio F-test. Ann Pharmacother, 2002 Jul-Aug, 36(7-8), 1162 - 7 Possible gatifloxacin-induced fulminant hepatic failure; Coleman CI et al.; OBJECTIVE: To report a case of fulminant hepatic failure associated with the use of gatifloxacin . CASE SUMMARY: A 76-year-old white man was found to have an approximate 1-week history of worsening jaundice on the last day of a 10-day course of gatifloxacin for treatment of impetigo while at his skilled nursing facility . Liver function tests including aspartate aminotransferase (AST), alanine aminotransferase (ALT), international normalized ratio, activated partial thromboplastin time, and ammonia concentrations were found to be markedly elevated, consistent with hepatocellular necrosis commonly seen with fluoroquinolones . Screening for other causes of hepatotoxicity, including alcoholic or viral hepatitis, obstruction, or autoimmune-mediated processes, were negative . Other potential medication causes were less likely . The patient's liver function steadily declined, eventually resulting in multiple organ failure . The patient died 25 days after completing the course of gatifloxacin . DISCUSSION: This case of hepatotoxicity was associated with gatifloxacin . Other fluoroquinolones, most notably trovafloxacin, have been observed to cause variable degrees of hepatotoxicity, ranging from asymptomatic elevations of liver enzymes to fulminant hepatic failure . Fluoroquinolones are thought to cause hepatocellular necrosis, which results in elevated ALT and AST concentrations with a normal alkaline phosphatase concentration . A variable degree of hyperbilirubinemia is often seen, with the presence and degree of jaundice often correlating to a poorer prognosis . Hepatic encephalopathy and coagulopathy are also commonly present . CONCLUSIONS: Fluoroquinolones, including trovafloxacin, ciprofloxacin, ofloxacin, enoxacin, norfloxacin, and, in this case report, gatifloxacin, have been associated with hepatotoxicity . It is important that these medications be considered a possible cause when the patient being treated has liver disease. Infez Med, 2001 Mar, 9(1), 39 - 42 Transverse myelitis associated with Mycoplasma pneumoniae pneumonitis: a report of two cases; Parisi A et al.; The authors report two cases of transverse myelitis due to Mycoplasma pneumoniae occurring during a recent acute infection due to Epstein-Barr virus (EBV) . The clinical picture included weakness of the legs, bladder dysfunction, fever, headache and in one case, a mild confusional state . Magnetic Resonance Imaging (MRI) revealed a segmental edema of the lumbar tract and cerebro-spinal fluid analysis showed a mild pleocytosis and an increased level of proteins with a blood-brain barrier damage . The diagnosis of acute infection due to Mycoplasma pneumoniae was made on serological criteria . The patients recovered completely after a 14-day course of an associated regimen with Ciprofloxacin (400 mg/day i.v.) plus prednisone (60 mg/day i.v.) . The authors emphasise the immunological disorders in the combined infection with Mycoplasma pneumoniae and EBV, supposing that an infective mononucleosis may predispose to mycoplasmic transverse myelitis. Int J Oncol, 2002 Jul, 21(1), 207 - 11 Ciprofloxacin inhibits cell growth and synergises the effect of etoposide in hormone resistant prostate cancer cells; El-Rayes BF et al.; Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer related deaths in men in the United States . Ciprofloxacin is a relatively non-toxic antibiotic that can be easily administered orally with large volume of distribution and good tissue penetration . Studies from others and our laboratory have recently reported its anti-tumor activity in a variety of human tumor cells . In our current experiment, we studied the effect of ciprofloxacin on a hormone resistant prostate cancer (HRPC) cell line, PC-3 . Our study shows significant in vitro cell growth inhibition of PC-3 cell line (p=0.0001) and also shows that there is a synergistic increase in the antiproliferative effect of etoposide when these cells are pretreated with ciprofloxacin for 24 h, prior to etoposide exposure (p=0.0001) . Western blot analysis of the protein extracts from these cells showed down-regulation of Bcl-2, altering the ratio of Bax:Bcl-2 favoring apoptosis . In our study no significant effect was seen on p21WAF1 expression by the combination of ciprofloxacin and etoposide but there was down-regulation of p21WAF1 gene by ciprofloxacin alone . Ciprofloxacin also inhibited NF-kappaB binding to DNA . Further studies in this area are warranted as the roles of p21WAF1, Bax/Bcl-2 and NF-kappaB may be important molecular events in mediating the antiproliferative and apoptosis inducing effect of etoposide in combination with ciprofloxacin in HRPC cells. Drug Dev Ind Pharm, 2002 Apr, 28(4), 423 - 9 Bioequivalence of two brands of ciprofloxacin 750 mg tablets (Sarf and Ciprobay) in healthy human volunteers; Abdallah RM et al.; An open, randomized, two-way crossover study was carried out in 28 healthy volunteers at Gulf Pharmaceutical Industries (Julphar), as a joint venture with Saqr Hospital, Ras Al-Khaimah, UAE . The two commercial brands used were Sarf (Julphar, UAE) as test and Ciprobay (Bayer AG, Germany) as reference product . The drug was administered to each subject with 240 mL of water after an overnight fasting in two treatment days separated by a one-week washout period . After dosing, serial blood samples were collected for a period of 24 hr and serum was separated and analyzed for ciprofloxacin using a sensitive, reproducible, and accurate high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection . Various pharmacokinetic parameters, including AUC0-t, AUC0-infinity, Cmax, Tmax, t1/2, and lambdaz, were determined from ciprofloxacin serum concentration-time profiles for both formulations and found to be in good agreement with reported values . The parameters AUC0-t, AUC0-infinity, and Cmax were tested for bioequivalence after log-transformation of data . No significant difference was found based on analysis of variance (ANOVA); the 90% confidence intervals (95.73-107.62%, 94.98-108.26%, 92.80-103.90% for AUC0-t, AUC0-infinity, Cmax, respectively) for the test/reference ratios of these parameters were within the bioequivalence acceptance range of 80-125% . Based on this data, it is concluded that both formulations are bioequivalent and are interchangeable in medical practice. Aliment Pharmacol Ther, 2002 Jul, 16 Suppl 4, 13 - 9 Review article: treatment of mild to moderate ulcerative colitis and pouchitis; Gionchetti P et al.; The meta-analyses of published trials have shown topical therapy with 5-aminosalicylic acid (5-ASA) to be the treatment of choice in active distal ulcerative colitis . Oral aminosalicylates are effective for both distal and extensive ulcerative colitis, but in distal colitis the rates of improvement and remission are usually lower than those reported for rectal 5-ASA therapy . An alternative to 5-ASA therapy is represented by the new steroids; budesonide and beclometasone dipropionate (BDP) enemas, the most extensively studied, have been shown to be as effective as conventional steroids but with a significantly lower inhibition of plasma cortisol . Patients who do not respond to 5-ASA or new steroids should be treated with oral steroids . Azathioprine or 6-mercaptopurine may be effective in patients who do not respond or cannot be weaned off steroids . Treatment of pouchitis is largely empirical and few controlled studies have been carried-out . Antibiotics are the treatment of choice and most patients make a good response to metronidazole or ciprofloxacin . Chronic refractory pouchitis may benefit from a prolonged course of a combination of antibiotics . Highly concentrated probiotics (VSL#3) are effective both for the prevention of pouchitis onset and the prevention of relapses. J Craniofac Surg, 2002 May, 13(3), 427 - 33 Bioabsorbable ciprofloxacin-containing and plain self-reinforced polylactide-polyglycolide 80/20 screws: pullout strength properties in human cadaver parietal bones; Tiainen J et al.; The aim of this study was to compare the pullout forces of recently developed bioabsorbable ciprofloxacin-containing and plain self-reinforced polylactide/polyglycolide (SR-PLGA) miniscrews in human cadaver parietal bones . Parietal bone pieces (approximately 6 x 20 cm) were collected from five human male cadavers (44-75 years of age) . Fifty plain SR-PLGA 80/20 miniscrews (diameter = 1.5 mm, length = 4.0 mm) and 50 ciprofloxacin-containing SR-PLGA 80/20 miniscrews (diameter = 1.5 mm, length = 4.0 mm) were used in this study . The force needed to pull the screws from human parietal cadaver bones was measured using a tensile strength-testing machine . The screw pullout speed was 10 mm/min . Means and SDs were calculated and analyzed using the Student t test (SPSS version 10.0 for Windows) . The pullout forces of the ciprofloxacin-containing and plain miniscrews were 66.8 +/- 4.9 N and 96.3 +/- 9.3 N (significant difference, P < 0.001), respectively . The most common cause of failure was screw-shaft breakage (60% in the case of ciprofloxacin-containing screws and 52% in the case of plain SR-PLGA screws) . Scanning electron microscopy showed that the fibrillar strip-like microstructure of plain SR-PLGA miniscrews turns into a coarse, uniaxial, platelet-like morphology in antibiotic SR-PLGA miniscrews as a result of the addition of ciprofloxacin . Ciprofloxacin-containing SR-PLGA screws consequently have a lower pullout strength than corresponding plain conventional SR-PLGA screws . Nevertheless, it is evident that the ciprofloxacin-containing screws can be applied in craniomaxillofacial surgery in nonload-bearing or slightly load-bearing applications. J Antimicrob Chemother, 2002 Jun, 49(6), 953 - 9 Regulation of fluoroquinolone uptake by human neutrophils: involvement of mitogen-activated protein kinase; Hotta K et al.; Although human neutrophils actively internalize fluoroquinolones, the precise uptake mechanism is not fully understood . In this study, we investigated the role of protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) in fluoroquinolone uptake in neutrophils . Spontaneous grepafloxacin uptake was significantly enhanced by SB203580, a p38 MAPK inhibitor, in a dose-dependent manner, but not by PD98059, a specific inhibitor of the upstream kinase that activates p44/42 MAPK . Neither inhibitor affected spontaneous ciprofloxacin or ofloxacin uptake . Phorbol myristate acetate (PMA) treatment enhanced ciprofloxacin uptake, whereas it reduced grepafloxacin uptake . These effects by PMA were significantly inhibited by the pretreatment of neutrophils with GF109203X, a specific inhibitor of PKC . PMA had no effect on ofloxacin uptake . The PMA-induced enhancement of ciprofloxacin uptake was inhibited by PD98059, but not by SB203580 . On the other hand, the PMA-induced reduction of grepafloxacin uptake was not inhibited by either MAPK inhibitor . Grepafloxacin, but not ciprofloxacin or ofloxacin, strongly phosphorylated p38 MAPK . This phosphorylation of p38 MAPK was not inhibited by GF109203X pretreatment . None of these three fluoroquinolones phosphorylated p44/42 MAPK . PMA phosphorylated both p38 and p44/42 MAPK . These findings indicate that grepafloxacin negatively regulates its uptake in neutrophils, and p38 MAPK activation is involved in this down-regulation of grepafloxacin uptake . Ciprofloxacin uptake is positively regulated by the activation of PKC, and p44/42 MAPK activation is involved in this up-regulation . Neither PKC, p38 nor p44/42 MAPK is involved in the regulation of ofloxacin uptake. Scand J Urol Nephrol, 2002, 36(2), 156 - 7 Acute bacterial endocarditis secondary to transrectal ultrasound-guided prostatic biopsy; Irani J et al.; We report the first case of a patient with no history of diabetes or cardiac problems who developed an endocarditis secondary to a transrectal prostatic biopsy . Urinalysis prior to the biopsy was normal and the patient had a course of ciprofloxacin 2 hours preoperatively. Ann Pharmacother, 2002 Jun, 36(6), 1000 - 2 Ciprofloxacin-associated hemolytic-uremic syndrome; Allan DS et al.; OBJECTIVE: To report the first case of ciprofloxacin-associated hemolytic-uremic syndrome (HUS) . CASE SUMMARY: A 53-year-old white man was treated with chemotherapy for acute lymphoblastic leukemia . Four weeks after initiation of treatment, he recovered his blood cell counts, but developed fever and was prescribed oral ciprofloxacin 500 mg twice daily . After 4 doses, he developed the typical features of HUS manifested by microangiopathic hemolytic anemia, oliguric renal failure, and thrombocytopenia . The medication was withdrawn, and he received 5 sessions of plasma exchange . He recovered completely and has normal renal function . DISCUSSION: Secondary HUS or its related syndrome, thrombotic thrombocytopenic purpura (TTP), is uncommon, but has been reported in association with cancer, chemotherapy, and a variety of medications . Our case represents a possible adverse drug reaction to ciprofloxacin according to the Naranjo probability scale . It is the first reported case of HUS associated with ciprofloxacin . CONCLUSIONS: Ciprofloxacin use was followed by HUS in our patient and was possibly causally related . Early detection, discontinuation of the offending medication, and treatment of HUS/TTP is critical. Antimicrob Agents Chemother, 2002 Jun, 46(6), 1980 - 4 Effect of ciprofloxacin on killing of Actinobacillus actinomycetemcomitans by polymorphonuclear leukocytes; Cacchillo DA et al.; Actinobacillus actinomycetemcomitans, a pathogen associated with aggressive periodontitis, resists phagocytic killing by polymorphonuclear leukocytes (PMNs) . It is susceptible to ciprofloxacin, which PMNs actively accumulate . This study tested the hypothesis that ciprofloxacin-loaded PMNs are more effective at killing A . actinomycetemcomitans than control PMNs . Isolated human PMNs were loaded by brief incubation with 0.5 microg of ciprofloxacin/ml . Opsonized bacteria (ATCC 43718) were incubated at 37 degrees C with control and ciprofloxacin-loaded PMNs and in the presence and absence of 0.5 microg of ciprofloxacin/ml . When assayed at bacteria-to-PMN ratios of 30:1 and 90:1, ciprofloxacin-loaded PMNs killed significantly more bacteria and achieved significantly shorter half times for killing than control PMNs (P < 0.05; Tukey's test) . At ratios of 3:1 and 10:1, these differences were not significant. Yao Xue Xue Bao, 1998 Dec, 33(12), 937 - 40 {Determination of levofloxacin in plasma and cerebrospinal fluid with HPLC and its pharmacokinetics in patients undergoing neurosurgical operations}; Luo S et al.; A RP-HPLC method was developed to determine the concentrations of levofloxacin in plasma and cerebrospinal fluid and its pharmacokinetics were studied in patients undergoing neurosurgical operations . C18H37 column was eluted with the mobile phase consisting of 10 mmol.L-1 KH2PO4-10 mmol.L-1(C4H9)4Br-CH3CN(45:45:10, pH 3.0) and the utraviolet absorbance was monitored at 295 nm . Ciprofloxacin was used as internal standard . The mean recoveries were 74.76% in plasma and 82.43% in cerebrospinal fluid, with the lowest detectable limits of 10 micrograms.L-1 and 6 micrograms.L-1, respectively . The RSD for the intra-day and inter-day were all less than 5% . A single oral administration of 300 mg levofloxacin tablet was given to 10 patients undergoing neurosurgical operations . The pharmacokinetic parameters in blood and in cerebrospinal fluid could be described by one compartment open model . The pharmacokinetic parameters were: blood Ke 0.12 +/- 0.04 h-1, T1/2 6.05 +/- 1.68 h, Tmax 1.05 +/- 0.29 h, Cmax 3.67 +/- 0.42 mg.L-1, AUC 33.43 +/- 7.32 mg.h.L-1, CLs 9.46 +/- 2.53 L.h-1, Vd 77.49 +/- 7.39 L; cerebrospinal fluid Ke 0.11 +/- 0.04 h-1, T1/2 6.95 +/- 1.88 h, Tmax 3.56 +/- 1.24 h, Cmax 1.68 +/- 0.25 mg.L-1, AUC 23.70 +/- 5.62 mg.h.L-1, CLs 13.70 +/- 5.11 L.h-1, Vd 126.61 +/- 13.20 L. J Chromatogr B Analyt Technol Biomed Life Sci, 2002 May 25, 772(1), 163 - 72 Determination of ciprofloxacin, enrofloxacin and flumequine in pig plasma samples by capillary isotachophoresis--capillary zone electrophoresis; Hernandez M et al.; Quinolones are a group of synthetic antibiotics that are widely used in veterinary medicine . Their residues may remain in tissues, milk, etc . intended for human consumption . The European Union fixes the maximum residue limits (MRLs) of veterinary medicinal products in foodstuffs of animal origin . Analytical methods are therefore needed to determine them in biological samples . In this study, we describe capillary isotachophoresis-capillary zone electrophoresis (ITP-CZE) to analyze three quinolones, enrofloxacin (ENR), ciprofloxacin (CPR) and flumequine (FLU), in pig plasma samples . We used solid-phase extraction with Oasis HLB cartridges as a sample pretreatment clean-up step . Capillary zone electrophoresis (CZE) requires low amounts of sample and is not as sensitive as one would wish . ITP-CZE is an easy way to increase the sample loadability and sensitivity . With this system sensitivity increases 40-fold . The detection limits for CPR, ENR and FLU were 70, 85 and 50 microg l(-1), respectively, which were lower than their MRLs in different kinds of samples . This method is simple and sensitive, and is therefore an alternative tool to the existing HPLC methods for analyzing the residuals of these quinolones in biological samples. J Chromatogr B Analyt Technol Biomed Life Sci, 2002 May 25, 772(1), 53 - 63 Separation of levofloxacin, ciprofloxacin, gatifloxacin, moxifloxacin, trovafloxacin and cinoxacin by high-performance liquid chromatography: application to levofloxacin determination in human plasma; Liang H et al.; A selective, sensitive and accurate liquid chromatographic method with UV and fluorescence detection was developed, validated and applied for the determination of fluoroquinolones in human plasma . The effects of mobile phase composition, ion-pair and competing-base reagents, buffers, pH, and acetonitrile concentrations were investigated on the separation of six quinolones (cinoxacin, levofloxacin, ciprofloxacin, gatifloxacin, moxifloxacin and trovafloxacin) . Sample preparation was carried out by adding internal standard and displacing agent and processing by ultrafiltration . This method uses ultraviolet and fluorescence detection and separation using a C(18) column . The recovery, selectivity, linearity, precision, and accuracy of the method were evaluated from spiked human plasma samples . The method was successfully applied to patient plasma samples in support of a levofloxacin pharmacokinetic study. Int J STD AIDS, 2002 Jun, 13(6), 416 - 9 Chronic prostatitis/chronic pelvic pain syndrome: national survey of genitourinary medicine clinics; Luzzi GA et al.; We sought to determine current practice in the diagnosis and management of chronic prostatitis/chronic pelvic pain syndrome (CPPS) in genitourinary medicine departments in the UK, using a detailed questionnaire survey . Evaluable responses were received from 147 (69%) clinics . Seventy-nine (54%) clinics reported seeing >10 new CPPS patients per year . A broad range of investigations was reported to be used in the diagnosis of CPPS . Whilst 89 (61%) clinics reported using the four-glass test in diagnosis, 46 (32%) reported using the test in >90% of patients with CPPS, and 42 (29%) reported never using the test . In the treatment, doxycycline or ciprofloxacin were reported to be first line treatment by 98% clinics, mostly in 4-6 week courses; however, great variation was recorded in second-line choices and use of non-antibiotic approaches . This survey demonstrates that patients with CPPS are regularly diagnosed and managed in genitourinary clinics in the UK, with wide variations in diagnostic and treatment practices. J Antimicrob Chemother, 2002 May, 49(5), 875 - 8 A randomized controlled trial of azithromycin versus doxycycline/ciprofloxacin for the syndromic management of sexually transmitted infections in a resource-poor setting; Rustomjee R et al.; A randomized controlled trial was carried out to assess the effectiveness of azithromycin versus a standard regimen with doxycycline/ciprofloxacin in the treatment of sexually transmitted infections in a resource-poor environment . Infection with Chlamydia trachomatis was cured in 23/24 (95.8%) of women in the azithromycin arm versus 19/21 (90.5%) in the doxycycline arm (P = 0.6), resulting in three treatment failures . Gonorrhoea was cured in 55/56 (98.2%) women, with one treatment failure in a patient with concomitant C . trachomatis infection . These results indicate that a single oral dose of azithromycin may prove to be a more effective and convenient treatment for sexually transmitted infections in women in a resource-poor environment J Antimicrob Chemother, 2002 May, 49(5), 827 - 30 The successful introduction of a programme to reduce the use of i.v . ciprofloxacin in hospital; Weller TM; The effectiveness of a programme to reduce the use of i.v . ciprofloxacin was assessed . i.v . ciprofloxacin was removed from ward stock and discussion occurred regarding appropriate use of the drug . Six months later, a factsheet containing recommendations was distributed to all medical staff and a requirement for justification before prescription was introduced . The programme reduced expenditure on i.v . ciprofloxacin to 34% of original levels . Savings of > 36,000 pounds sterling were made for two consecutive years . A sustained reduction in the use of i.v . ciprofloxacin was obtained by a combination of education and restriction. Am J Gastroenterol, 2002 Apr, 97(4), 972 - 7 Irritable pouch syndrome: a new category of diagnosis for symptomatic patients with ileal pouch-anal anastomosis; Shen B et al.; OBJECTIVE: Pouchitis often is diagnosed based on symptoms alone . However, increased stool frequency, urgency, and abdominal pain could be due to a condition resembling irritable bowel syndrome . This study was designed to assess the etiology of bowel symptoms using the Pouchitis Disease Activity Index (PDAI) . METHODS: Symptoms, endoscopy, and histology were assessed in 61 consecutive symptomatic patients with ulcerative colitis after ileal pouch-anal anastomosis . Pouchitis was defined as a PDAI score of > or = 7, cuffitis was defined as endoscopic and histological inflammation of the rectal cuff and no inflammation of the pouch, and irritable pouch syndrome (IPS) was defined as symptoms with a PDAI of <7 and the absence of cuffitis . RESULTS: Thirty-one patients (50.8%) had pouchitis, four (6.5%) had cuffitis, and 26 (42.6%) had IPS . Demographics were similar in the three groups . Increased stool frequency, urgency, and abdominal cramps were the most common symptoms in the three groups . Rectal bleeding was seen only in cuffitis (p < 0.001) . No patient in the three groups had fever . Twenty-seven patients (87.1%) with pouchitis responded to a 2-wk course of ciprofloxacin or metronidazole with a reduction in PDAI scores of > or = 3 . All four patients with cuffitis responded to topical hydrocortisone or mesalamine with a reduction in the PDAI symptom component score of > or = 1 . Twelve patients with IPS (46.2%) responded to antidiarrheal, anticholinergic, and/or antidepressant therapies with a reduction in the PDAI symptom component score of > or = 1, whereas the remaining patients had persistent symptoms despite therapy . CONCLUSIONS: A substantial number of symptomatic patients after ileal pouch-anal anastomosis do not meet the diagnostic criteria for either pouchitis or cuffitis and have been classified as having IPS . There is an overlap of symptoms among patients with pouchitis, cuffitis, and IPS, and endoscopic evaluation can differentiate among these groups . Distinction between these three groups has therapeutic implications. Nucleic Acids Res, 2002 May 15, 30(10), 2144 - 53 Functional characterisation of mycobacterial DNA gyrase: an efficient decatenase; Manjunatha UH et al.; A rapid single step immunoaffinity purification procedure is described for Mycobacterium smegmatis DNA gyrase . The mycobacterial enzyme is a 340 kDa heterotetrameric protein comprising two subunits each of GyrA and GyrB, exhibiting subtle differences and similarities to the well-characterised Escherichia coli gyrase . In contrast to E.coli gyrase, the M.smegmatis enzyme exhibits strong decatenase activity at physiological Mg2+ concentrations . Further, the enzymes exhibited marked differences in ATPase activity, DNA binding characteristics and susceptibility to fluoroquinolones . The holoenzyme showed very low intrinsic ATPase activity and was stimulated 20-fold in the presence of DNA . The DNA-stimulated ATPase kinetics revealed apparent K0.5 and kcat of 0.68 mM and 0.39 s(-1), respectively . The dissociation constant for DNA was found to be 9.2 nM, which is 20 times weaker than that of E.coli DNA gyrase . The differences between the enzymes were further substantiated as they exhibited varied sensitivity to moxifloxacin and ciprofloxacin . In spite of these differences, mycobacterial DNA gyrase is a functionally and mechanistically conserved enzyme and the variations in activity seem to reflect functional optimisation for its physiological role during mycobacterial genome replication. Leuk Lymphoma, 2002 Feb, 43(2), 451 - 3 Acute myeloblastic leukemia achieving complete remission with amifostine alone; Ozturk A et al.; Amifostine, a phosphorylated thiol-amine, is known as a cytoprotective agent especially for cisplatin containing chemotherapies . Apart from the cytoprotective role, Amifostine could also be used in the treatment of hematologic malignancies such as myelodysplastic syndrome (MDS) and acute myeloblastic leukemia (AML), as a treatment option or for potentiating the effects of cytotoxic agents . We tried to use Amifostine in a patient with AML, which did not respond to conventional cytotoxic chemotherapy and aimed to publish the results . The patient was a 77-year-old male patient, he was diagnosed as AML by peripheral blood smear and bone marrow aspiration . Treatment commenced with low dose cytosine arabinoside (Ara-C) but the therapy should have ceased due to patient intolerance . The patient refused further therapy and he was offered to have Amifostine treatment . Amifostine was administered 200 mg/m2 three times a week, with ciprofloxacin, pentoxifyllin and dexamethasone . Dramatic response was obtained after 8 weeks of administration . Blast rate was reduced from 35 to 7% in bone marrow aspiration; pancytopenia was restored to normal levels . This remission was maintained through 8 more weeks . Amifostine treatment was restarted after he relapsed but this time he did not respond to the treatment and died of gastrointestinal bleeding on the 8th week of treatment. Indian J Gastroenterol, 2002 Mar-Apr, 21(2), 62 - 3 Pharmacokinetics of ciprofloxacin in patients with liver cirrhosis; Dixit RK et al.; BACKGROUND: Bacterial infections are common in patients with cirrhosis of liver and are frequently treated with ciprofloxacin . Literature on pharmacokinetics of ciprofloxacin in patients with cirrhosis of the liver is scanty . The present study compared the pharmacokinetics of ciprofloxacin in cirrhotic patients with that in healthy volunteers . METHODS: In 20 patients with cirrhosis of liver (all Child-Pugh class B) and 10 healthy volunteers, plasma levels of ciprofloxacin were measured using high-performance liquid chromatography at several time points after a 500-mg oral dose . Various pharmacokinetic parameters were calculated . RESULTS: No significant differences were observed in maximum plasma levels reached (mean {SD} 2.6 {0.6} vs 2.6 {1.3} microg/ml), time taken for maximum plasma levels to be reached (1.3 {0.6} vs 1.5 {0.9} h), t1/2a (0.7 {0.3} vs 0.4 {0.9} h), elimination half-life (3.6 {1.2} vs 3.2 {1.8} h), and area under the curve (19.3 {3.8} vs 21.9 {4.5} microg/mL x h) in healthy volunteers and cirrhotic patients, respectively . CONCLUSIONS: Pharmacokinetics of ciprofloxacin is unaltered in patients with liver cirrhosis . Ciprofloxacin can be safely administered in the usual doses in such patients. J Pediatr Hematol Oncol, 2002 May, 24(4), 321 - 2 Interaction between methotrexate and ciprofloxacin; Dalle JH et al.; High-dose methotrexate is used in malignant hemopathies and solid tumors in children . Methotrexate serum concentrations must be monitored because of the possible toxicity of drug elimination delay . Several drugs (e.g., penicillin, probenecid) can alter the elimination of methotrexate . The authors report two cases of delayed elimination of methotrexate in patients receiving ciprofloxacin, with severe toxicity. Aliment Pharmacol Ther, 2002 May, 16(5), 909 - 17 Four-week open-label trial of metronidazole and ciprofloxacin for the treatment of recurrent or refractory pouchitis; Mimura T et al.; BACKGROUND: Preliminary data suggest that short-term antibiotic therapy with a single drug is effective for the treatment of patients with pouchitis . However, some patients are resistant to treatment . AIM: To evaluate the therapeutic efficacy of a prolonged course of a combination of two antibiotics in patients with refractory or recurrent pouchitis, as well as its impact on their quality of life . METHODS: Patients with active refractory or recurrent pouchitis were recruited . This was defined as both: (i) a history of pouchitis at least twice in the last 12 months or persistent pouchitis requiring continual intake of antibiotics; and (ii) a Pouchitis Disease Activity Index score 3 7 (best to worst pouchitis=0-18) at the beginning of therapy . Treatment consisted of a combination of metronidazole, 400 or 500 mg twice daily, and ciprofloxacin, 500 mg twice daily, for 28 days . Symptomatic, endoscopic and histological evaluations were undertaken before and after antibiotic therapy using the Pouchitis Disease Activity Index score . Remission was defined as a combination of a Pouchitis Disease Activity Index clinical score of <or= 2, endoscopic score of <or= 1 and total score of <or= 4 . The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire, which encompasses bowel, systemic and emotional symptoms as well as social function (worst to best=32-224) . RESULTS: Forty-four patients (24 male, 20 female; median age, 37.5 years) entered the trial and completed treatment . Thirty-six (82%) went into remission . The median Pouchitis Disease Activity Index scores before and after therapy were 12 (range, 8-17) and 3 (range, 1-10), respectively (P < 0.0001) . The median Inflammatory Bowel Disease Questionnaire score also significantly improved from 96.5 (range, 74-183) to 175 (range, 76-215) with this therapy (P < 0.0001) . The eight patients (five male, three female) who did not go into remission were significantly older (median 47.5 vs . 35 years; P=0.007), had a longer history of pouchitis (95.5 vs . 26 months; P=0.0008), had a greater proportion with chronic pouchitis (chronic/relapsing: 6/2 vs . 9/27; relative risk, 1.6; 95% confidence interval, 1.0-2.4) and tended to have a higher Pouchitis Disease Activity Index score before treatment (median 14.5 vs . 12; P=0.13) than those who went into remission . Even in these eight patients, the median Pouchitis Disease Activity Index score significantly improved from 14.5 (range, 8-16) to 9.5 (range, 7-10) (P=0.0078), as did the Inflammatory Bowel Disease Questionnaire score from 95.5 (range, 74-134) to 127 (range, 76-187) (P=0.039) . The Inflammatory Bowel Disease Questionnaire score strongly correlated with the Pouchitis Disease Activity Index score (r=0.79, P < 0.0001), and was significantly related to the patients' overall assessment of satisfaction (P < 0.0001) . No serious side-effects were noted . CONCLUSIONS: Four-week treatment with a combination of metronidazole and ciprofloxacin is highly effective in patients with active recurrent or refractory pouchitis, objectively improving the inflammation and quality of life . The Inflammatory Bowel Disease Questionnaire is a sensitive tool for evaluating patients with pouchitis, and correlates well with disease activity. J Vet Med A Physiol Pathol Clin Med, 2002 Mar, 49(2), 99 - 104 Concentration of enrofloxacin and its metabolite ciprofloxacin in canine matrices of the locomotor system; Ehinger AM et al.; Due to its pharmacodynamic and pharmacokinetic properties, the use of enrofloxacin may be indicated in canine osteomyelitis, but there is insufficient data on its distribution within the musculoskeletal tissues . The dogs used in this study were 31 regular veterinary orthopaedic patients . Four hours after their oral or subcutaneous treatment with 10 mg/kg enrofloxacin (Baytril; Bayer, Leverkusen, Germany) once daily for 1 or 3 days, the concentration of enrofloxacin and its main metabolite ciprofloxacin was quantified in plasma, bone, musculature and other matrices of the locomotor system by high pressure liquid chromatography with fluorescence-detection after homogenization and solid phase extraction of the samples . By oral or subcutaneous administration of enrofloxacin once daily for 3 days, higher concentrations of the active constituents in the samples were achieved than by single treatment . Nevertheless, even after single injection, minimal inhibitory enrofloxacin concentrations of up to 0.5 microg ml or microg/g sample against most pathogens of osteomyelitis were exceeded . In the musculature, on average, higher concentrations of active constituents were detected than in less perfused matrices (bones and synovial membranes) at sampling time . The enrofloxacin diffusion into inflamed bone was higher compared with mechanically damaged bone, whereas for ciprofloxacin it was lower . In conclusion, a dosage of 10 mg/kg enrofloxacin is sufficient to exceed the minimal inhibitory concentrations in osteomyelitic bone against most pathogens that are sensitive in vitro, but clinical efficacy remains to be evaluated. Eur Respir J, 2002 Mar, 19(3), 469 - 71 Achilles tendon disease in lung transplant recipients: association with ciprofloxacin; Chhajed PN et al.; Achilles tendonitis or rupture are uncommon complications following the use of fluoroquinolones, with a reported incidence in the general population of 0.4% . The aims of the current study were to determine the incidence of Achilles tendon disease (ATD) in lung transplant recipients (LTR) and to identify risk factors . Questionnaires were sent to 150 LTR of whom 101 responded (67%) . Twenty-two LTR (21.8%) experienced ATD (tendonitis 16, rupture six) . The mean age of LTR who developed ATD was 52.9+/-6.1 yrs (range: 19-63.5 yrs) . Only the use of ciprofloxacin was significantly associated with ATD (p<0.05) . Age, sex, underlying disease necessitating transplantation, serum creatinine and cyclosporine levels were not associated with ATD . The association between ciprofloxacin and ATD was not dose related . Of the 72 LTR who had received ciprofloxacin, 20 (28%) developed ATD (tendonitis 15, rupture five) . In patients receiving ciprofloxacin, there was no association between the mean cumulative dose of prednisolone and ATD . Tendon rupture occurred with a lower ciprofloxacin dosage than tendonitis and the mean recovery duration was significantly longer . To conclude, lung transplant recipients receiving ciprofloxacin are at significant risk of developing Achilles tendon disease . The association between ciprofloxacin and Achilles tendon disease appears to be idiosyncratic rather than dose-related. Dtsch Med Wochenschr, 2002 Apr 5, 127(14), 735 - 8 {Skin nodules and ulcers of the limbs in a patient with rheumatoid arthritis}; Bocher W et al.; CASE HISTORY: While being treated with corticosteroids and methotrexate for rheumatoid arthritis, a 63-year-old man developed livid nodules on his lower arms, hands and feet, as well as fever, necrotizing skin ulcers and rupture of a finger extensor tendon . INVESTIGATIONS: No vasculitis was found in a biopsy of one of the nodules on the lower arm . Fast growing mycobacteria, classified as M . marinum by PCR, were cultured from wound swabs . Treatment and course: The lesions healed on administration of ciprofloxacin, ethambutol and clarithromycin as well as local treatment . CONCLUSION: Cutaneous lesions of an atypical mycobacterial infection are often misdiagnosed . This is especially so in immunocompromised patients and in the differential diagnosis of vasculitis. Chin Med J (Engl), 2002 Jan, 115(1), 31 - 5 Accumulation of ciprofloxacin and lomefloxacinin fluoroquinolone-resistant strains of Escherichia coli; Xia P et al.; OBJECTIVE: To evaluate the role of outer membrane protein (Omp) F-deficiency and active efflux in the accumulation of hydrophilic fluoroquinolones ciprofloxacin (CPLX) and lomefloxacin (LMLX) in resistant E . coli strains . METHODS: Fluoroquinolone accumulation in bacteria and the effect of active efflux were measured by a fluorescence method . The outer membrane proteins of the bacteria were analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) . E . coli strains in this study included control strains JF701 and JF703 that are OmpC- or OmpF-deficient mutants of E . coli K-12, respectively, and the fluoroquinolone susceptible strain the fluoroquinolone susceptible strain of Escherichia coli (Ecs) and its in vitroselected resistant strains R2 and R256, and the clinical resistant isolates R5 and R6 . RESULTS: The steady-state accumulation concentration of each drug in Ecs appeared to be the same as in JF701, while in the OmpF-deficient strain JF703, it was 1/5 CPLX or 1/2 LMLX lower than that in JF701, but JF703 was still susceptible to fluoroquinolones . On the other hand, compared with susceptible strains, a 2- to 10-fold decrease in the accumulation of each drug was found in the resistant strains except R2, in which the accumulation was slightly higher than in JF703 . After the addition of 2,4-dinitrophenol (DNP), accumulation of each drug increased, especially in resistant strains, indicating that the function of the active efflux (pump) system in these bacteria had been enhanced dramatically . Furthermore, both OmpF and OmpC in Ecs, OmpF-deficiency in R2 and R256 and OmpC-deficiency in R5 and R6 were observed . CONCLUSION: The decreased accumulation of hydrophilic fluoroquinolones in E . coli involved OmpF-deficiency and active efflux (pump), and the latter may be an important factor. Scand J Infect Dis, 2002, 34(2), 136 - 7 Sinusitis due to Stenotrophomonas maltophilia; Gunnarsson G et al.; This is the first report of a patient diagnosed with sinusitis due to Stenotrophomonas maltophilia . Despite the organism being resistant to trimethoprim-sulfamethoxazole, the infection was cured by drainage and treatment with intravenous piperacillin, followed by oral ciprofloxacin. J Assoc Physicians India, 2002 Mar, 50, 430 - 1 Ciprofloxacin-induced QTc prolongation; Singh H et al.; Ciprofloxacin has been widely used for treating infections and has been found to have very low cardiovascular side effects . QTc prolongation with the use of ciprofloxacin is yet to be reported in literature . A case report highlighting QTc prolongation by use of ciprofloxacin is being presented. Nuklearmedizin, 2002 Feb, 41(1), 30 - 6 {Tc-99m ciprofloxacin in clinically selected patients for peripheral osteomyelitis, spondylodiscitis and fever of unknown origin--preliminary results}; Gallowitsch HJ et al.; AIM: Retrospective evaluation of Tc-99m ciprofloxacin (infection) scintigraphy consecutively performed in a series of patients clinically suspected for peripheral osteomyelitis (OM), spondylodiscitis (SD) and fever of unknown origin (FUO) . METHODS: A total of 20 patients clinically suspected for OM (n = 12), SD (n = 3) and FUO (n = 5) were included in our retrospective analysis . The additional criterion was a positive 3-phase bone scan for OM, or a 2-phase bone scan in case of SD . Planar whole body scans and static acquisitions were performed 1 and 4 h after application of 370 MBq Tc-99m ciprofloxacin . In 10 patients with suspected OM, additional immunoscintigraphy using Tc-99m labelled monoclonal antibodies (Mab BW 250/183) was performed and the correlation of infection to bloodpool and antigranulocyte scintigraphy was analysed . RESULTS: OM: Bacterial infection was confirmed in 8 of 15 lesions . Infection demonstrated true positive (TP) results in 7 of 8, true negative (TN) results in 2 of 7, false positive (FP) results in 5 of 7 patients and one false negative (FN) result . A strong correlation could be demonstrated between T/NT ratios of infection and bloodpool Tc-99m medronate imaging (r = 0.84, 0.88) and between infection and BW 250/183 (r = 0.92, 0.90) . Using a threshold of 2.0 for T/NT ratio, only TP results could be observed whereas a T/NT in the range of 1.0-2.0 could not discriminate between septic and aseptic inflammation . Concordant results with Mab BW 250/183 could only be observed in 5 of 10 patients (4 TP, 1 TN) by showing 4 FP and 1 FN lesions with IF . CONCLUSION: Non-specific uptake of infection can be observed in a variety of clinical situations with moderate uptake, by showing a strong correlation with blood-pool imaging . Nevertheless, intense uptake may be specific for septic inflammation. Eur J Nucl Med Mol Imaging, 2002 Apr, 29(4), 530 - 5 Epub 2002 Feb 26. Infecton is not specific for bacterial osteo-articular infective pathology; Dumarey N et al.; The aim of this study was to re-examine, by retrospective analysis of our case material, the specificity and sensitivity of technetium-99m ciprofloxacin scan in discriminating between infection and other conditions . (99m)Tc-ciprofloxacin scintigraphy was performed in 71 patients: 30 patients referred for suspicion of osteomyelitis (OM) or septic arthritis (SA) (group 1) and 41 controls (group 2) . Imaging was performed at 4 h post injection and, when possible, at 8 or 24 h post injection . Tracer uptake was visually assessed in different joint groups, and in the sites suspicious for infection . Several soft tissue sites were also evaluated . In the group referred for osteo-articular infection, we found a lower specificity (54.5%) than has previously been reported in the literature . Evaluation of tracer uptake at late imaging did not improve discrimination between sterile and non-sterile inflammation . Additionally, articular uptake was seen in many control patients . Infecton uptake in growth cartilage, thyroid gland, vascular pool, lungs, liver and intestines is discussed. Am J Ther, 2002 Mar-Apr, 9(2), 149 - 56 Important role of prodromal viral infections responsible for inhibition of xenobiotic metabolizing enzymes in the pathomechanism of idiopathic Reye's syndrome, Stevens-Johnson syndrome, autoimmune hepatitis, and hepatotoxicity of the therapeutic doses of acetaminophen used in genetically predisposed persons; Prandota J; Upper respiratory tract febrile illnesses caused by various viruses, mycoplasma, chlamydia infections, and/or inflammatory diseases are usually observed a few days to a few (several) weeks before the onset of Reye's syndrome, Stevens-Johnson syndrome, autoimmune hepatitis (hepatotropic virus infections), or hepatotoxicity associated with therapeutic administration of acetaminophen in persons with varying degrees of deficits of important enzymatic activity . Activation of systemic host defense mechanisms by inflammatory component(s) results in depression of various induced and constitutive isoforms of cytochrome P-450 mixed-function oxidase system superfamily enzymes in the liver and most other tissues of the body . Because several cytochrome P-450 enzymes activities important for biotransformation of many endogenous and egzogenous substances show considerable variability between individuals, in some genetically predisposed persons, even the administration of therapeutic doses of a drug may result in serious clinical mishaps, if an important concomitant risk factor (eg, acute viral infection) is involved . Several inflammatory cytokines, such as interleukins, transforming growth factor beta1, human hepatocyte growth factor, and lymphotoxin, downregulate gene expression of major cytochrome P-450 enzymes with the specific effects on mRNA levels, protein expression, and enzyme activity observed with a given cytokine varying for each P-450 studied, thus eventually leading to metabolite-mediated adverse drug reactions and immunometallic diseases which sometimes result in tissue injury beyond the site(s) where metabolic bioactivation takes place . On the other hand, it must be emphasized that inhibition of metabolism of several drugs, as well as influence on the concentration and/or ratio of various cytokines in inflamed tissues, may exert beneficial effects in patients with different diseases, thus opening new therapeutic possibilities . Clinically relevant interactions may be exemplified by the effects of some fluoroquinolone antibiotics, such as pefloxacin and ciprofloxacin, which probably have a steroid-sparing effect in some patients with frequently relapsing nephrotic syndrome, and an increased bioavailability of several drugs following concomitant intake with freshly pressed grapefruit juice, eventually caused by inhibition of their metabolism, mediated mainly by CYP3A and specifically inhibited by naturally occurring flavonoids. Res Vet Sci, 2001 Oct, 71(2), 101 - 9 Pharmacokinetics and residues of ciprofloxacin and its metabolites in broiler chickens; Anadon A et al.; The pharmacokinetic properties of ciprofloxacin and its metabolites were determined in healthy chickens after single i.v . and oral dosage of 8 mg ciprofloxacin kg(-1) bodyweight . After i.v . and oral administration, the plasma concentration-time graph was characteristic of a two-compartment open model . Mean (SD) elimination half-life and mean residence time of ciprofloxacin in plasma were 8.84 (2.13) and 8.54 (1.64) hours, respectively, after i.v . administration and 11.89 (1.95) and 13.32 (2.65) hours, respectively, after oral administration . Mean maximal plasma concentration of ciprofloxacin was 2.63 (0.20) microg ml(-1), and the interval from oral administration until maximum concentration was 0.36 (0.07) hours . The mean oral bioavailability of ciprofloxacin was found to be 69.12 (6.95) per cent . Ciprofloxacin was mainly converted to oxociprofloxacin and desethyleneciprofloxacin . Considerable kidney, liver, muscle and skin + fat tissue concentrations of ciprofloxacin and its metabolites oxociprofloxacin and desethyleneciprofloxacin were found when ciprofloxacin was administered orally (8 mg kg(-1) on 3 successive days) . It was estimated that mean tissue concentrations of ciprofloxacin and its metabolites ranging between 0.011 to 0.75 microg g(-1) persisted for 5 days. Antibiot Khimioter, 2001, 46(10), 11 - 3 {Comparative yearly growth rate of children with mucoviscidosis treated and not treated with ciprofloxacin:clinicomorphological comparisons}; Postnikov CC et al.; The results of the prospective and comparative investigation of the linear growth of children at the age of 4 to 16 years with mucoviscidosis treated with ciprofloxacin in combination with a cephalosporin or an aminoglycoside in the main group and a cephalosporin or an aminoglycoside alone in the control group are presented . The children were observed for 3 and 5 years . It was shown that in spite of the treatment term with ciprofloxacin the yearly growth rate in the children in the main and control groups did not significantly differ . The morphological investigation did not reveal any injury of the armicular cartilage and growth zone . The hyperplastic reaction in the tegmental cartilage was states and considered as a physiological one in response to the presence of ciprofloxacin and therefore reversible . No chondrotoxicity of the fluoroquinolones and ciprofloxacin, particularly in the children, is explained. Br J Pharmacol, 2002 Mar, 135(5), 1263 - 75 Multiple pathways for fluoroquinolone secretion by human intestinal epithelial (Caco-2) cells; Lowes S et al.; 1 . Human intestinal epithelial Caco-2 cells, T84 cells, and MDCKII cells transfected with human MDR1, were used to investigate the mechanistic basis of transintestinal fluoroquinolone secretion . 2 . The fluoroquinolone grepafloxacin was secreted across Caco-2 monolayers by a saturable process (V(max)=16.9 +/- 3.4 nmol.cm(-2).h(-1)) . Net secretion was reduced by 2-deoxyglucose/azide treatment to reduce intracellular ATP . 3 . Grepafloxacin inhibited {(14)C}-ciprofloxacin (100 microM) secretion across Caco-2 monolayers (K(0.5)=0.8 mM), and concurrently increased the cellular accumulation of ciprofloxacin from the basal medium, indicating inhibition of export across the apical membrane . 4 . The unconjugated bile acid, cholic acid, was secreted across Caco-2 monolayers, and this secretion was sensitive to inhibition by the MRP-selective inhibitor MK-571, suggesting MRP2 involvement . Secretion of cholic acid (10 microM) across the apical membrane was also inhibited by grepafloxacin (K(0.5)=0.3 mM), but not by ciprofloxacin . 5 . In MDCKII-MDR1 monolayers, net secretion of grepafloxacin was increased by 3.5 fold compared with untransfected controls . Neither ciprofloxacin nor cholic acid showed net secretion in either MDCKII or MDCKII-MDR1 monolayers, showing that in contrast to grepafloxacin, neither are substrates for MDR1 . 6 . In T84 monolayers, which express MDR1 but not MRP2, neither ciprofloxacin nor cholic acid was secreted, whilst the V(max) for grepafloxacin secretion was lower than in Caco-2 cells, which express both MDR1 and MRP2 . 7 . In conclusion, the transepithelial secretion of grepafloxacin is mediated by both MRP2 and MDR1, whereas ciprofloxacin is a substrate for neither . Grepafloxacin also competes for the ciprofloxacin-sensitive pathway, which remains to be elucidated. Arch Toxicol, 2002 Jan, 75(11-12), 725 - 33 Ultrastructural characterization of murine limb buds after in vitro exposure to grepafloxacin and other fluoroquinolones; Shakibaei M et al.; The effects of selected quinolones (levofloxacin, lomefloxacin, temafloxacin and grepafloxacin) on growth and differentiation of murine limb buds were studied in vitro . Ciprofloxacin and ofloxacin served as controls . We used limb buds from 12-day-old mouse embryos that were grown for 6 days in a serum-free, standard or magnesium-deficient medium . Besides evaluation under a dissecting microscope, we used electron microscopy to characterize the effects in detail . The following results are noteworthy . (1) Comparing the effects of standard and magnesium-deficient medium after 3 and 6 days in culture, we found ultrastructural changes after 6 days only . (2) Direct comparison of ofloxacin (racemate) and levofloxacin (L-enantiomer) showed that they had a similar, rather low, potential for affecting cartilage development . (3) The effects of temafloxacin and ciprofloxacin were more pronounced in magnesium-deficient medium, but those of the other drugs were not . (4) Grepafloxacin was the most active quinolone in this assay . It impaired growth and differentiation of limb buds at 30 mg/l; at higher concentrations the explants did not grow . With lower concentrations of 10 mg grepafloxacin/l, no effects were detectable under a dissecting microscope but characteristic changes were seen by electron microscopy . We observed electron-dense aggregates on and within chondrocytes, detachment of the cell membrane from the matrix with matrix-free pericellular areas around chondrocytes, and swelling of cell organelles such as mitochondria and rough endoplasmic reticulum . (5) The affinity of grepafloxacin for divalent cations (Mg2+, Ca2+) was studied by measuring the fluorescence of grepafloxacin solution at various concentrations of Mg2+ and Ca2+ . Grepafloxacin showed a relatively high affinity for Ca2+ in the fluorescence assay, which was more pronounced than the affinities of six other fluoroquinolones tested before. Br J Cancer, 2002 Feb 1, 86(3), 443 - 8 Ciprofloxacin induces apoptosis and inhibits proliferation of human colorectal carcinoma cells; Herold C et al.; Efficacy of chemotherapy in advanced stages of colorectal tumours is limited . The quinolone antibiotic ciprofloxacin was recently shown to inhibit growth and to induce apoptosis in human bladder carcinomas cells . We investigated the effect of ciprofloxacin on colon carcinoma lines in vitro . CC-531, SW-403 and HT-29 colon carcinoma and HepG2 hepatoma cells (control cells) were exposed to ciprofloxacin . Proliferation was assessed by bromodeoxyuridine-incorporation into DNA and apoptosis was measured by flow cytometry after propidium iodide or JC-1 staining . Expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax was analyzed by semiquantitative Western blot analysis and activity of caspases 3, 8 and 9 by substrate-cleavage assays . Ciprofloxacin suppressed DNA synthesis of all colon carcinoma cells time- and dose-dependently, whereas the hepatoma cells remained unaffected . Apoptosis reached its maximum between 200 and 500 microg ml(-1) . This was accompanied by an upregulation of Bax and of the activity of caspases 3, 8 and 9, and paralleled by a decrease of the mitochondrial membrane potential . Ciprofloxacin decreases proliferation and induces apoptosis of colon carcinoma cells, possibly in part by blocking mitochondrial DNA synthesis . Therefore, qualification of ciprofloxacin as adjunctive agent for colorectal cancer should be evaluated . Electrophoresis, 2002 Feb, 23(3), 506 - 11 Using nonaqueous capillary electrophoresis to analyze several quinolones in pig kidney samples; Hernandez M et al.; We show the potential of nonaqueous capillary electrophoresis (NACE) for analyzing enrofloxacin (ENR), ciprofloxacin (CPR), danofloxacin (DAN), difloxacin (DIF), marbofloxacin (MAR), flumequine (FLU), and oxolinic acid (OXA) in pig kidney samples . We have studied the effects of parameters such as the composition of the organic media, the choice of electrolyte, the pH* of the background electrolyte (BGE), the addition of modifiers, and the reversal of electroosmotic flow . Separation was good with 20 mM ammonium acetate, 0.004% polycation hexadimethrine bromide (HDB), and 4% acetic acid (pH* 5.4) in methanol/acetonitrile (50:50 v/v) medium . We used a quick and simple sample preparation method, hydrochloric acid as an extractant and solid-phase extraction (SPE) with Baker C18 cartridges as the cleanup step . Recoveries for all quinolones were over 80%. J Arthroplasty, 2002 Feb, 17(2), 230 - 4 Psoas abscess associated with infected total hip arthroplasty; Buttaro M et al.; A 65-year-old man with a left uncemented total hip arthroplasty performed 11 years previously was admitted with a history of progressive low back pain, left hip pain, and sepsis that had begun 6 months earlier . On physical examination, a gross, fluctuant mass was palpated in the left thigh . A computed tomography (CT) scan revealed a 6.5 x 3 cm left retrofascial psoas abscess communicating with the hip joint . The patient underwent irrigation and debridement of the hip with removal of the components . The psoas abscess was drained through the iliopsoas bursa . A residual psoas abscess was drained percutaneously under CT guidance . Cultures isolated Escherichia coli, and the patient responded to 6 months of ciprofloxacin therapy . After 1 year, the patient had no evidence of infection . Pathways of infection spread, diagnosis, and treatment of a patient with this rare association are discussed with a review of the literature. New Microbiol, 2002 Jan, 25(1), 97 - 102 Ralstonia pickettii bacteraemia in a cord blood transplant recipient; Woo PC et al.; A seven-year old boy with acute lymphoblastic leukemia underwent an HLA mismatched cord blood transplant . He developed grade 2 mucositis requiring morphine infusion and grade 3-4 hyperacute graft-versus-host disease affecting the skin, gastrointestinal tract, and liver requiring pulse methylprednisolone . On days 21, 23, and 24 post-transplant, blood culture obtained through the central line and periphery were positive for Ralstonia pickettii . The same strain (with the same biochemical profile and antibiotic susceptibility pattern) was also recovered from surveillance throat swab cultures from day 11 to day 24 and surveillance rectal swab cultures from day 16 to day 24 . The patient responded to intravenous cefoperazone/sulbactam and ciprofloxacin and blood culture became negative 3 days after commencement of the antibiotics . Although R . pickettii is of low virulence and is a frequent contaminant of blood cultures, it should not be overlooked when it is repeatedly recovered from sterile body fluids, especially in immunocompromised hosts. Inflamm Bowel Dis, 2002 Jan, 8(1), 10 - 5 Preliminary study of ciprofloxacin in active Crohn's disease; Arnold GL et al.; Based on limited reports of the successful use of antibiotics in the treatment of Crohn's disease (CD) and on the possibility that intestinal bacteria may be one of the etiologic factors playing a role in the pathogenesis of this condition, we undertook a study to evaluate the use of a broad-spectrum antibiotic in CD . Our team studied the efficacy of adding the antibiotic ciprofloxacin to the treatment of moderately active, but resistant cases of CD . Forty-seven adults with moderately active CD were randomly assigned treatment with ciprofloxacin 500 mg twice daily versus placebo twice daily for 6 months . The primary endpoint was the change in scores on the Crohn's Disease Activity Index (CDAI) from baseline to month 6 . Although 47 patients were randomized, at 1 month of follow-up 28 patients received ciprofloxacin and 19 received placebo . The mean entry CDAI scores were not significantly different: 187 for the ciprofloxacin group versus 230 for the placebo group (p = 0.638) . Mean CDAI scores at the completion of study were 112 for the ciprofloxacin group (n = 25) and 205 for the placebo group (n = 12), (p < 0.001) . Disease remission is defined as a decrease in the CDAI score to less than 150 points . Our preliminary study suggests that ciprofloxacin may be an effective agent when added to the treatment of moderately active, resistant CD. J Pharm Sci, 2002 Feb, 91(2), 482 - 91 A novel approach to the pulmonary delivery of liposomes in dry powder form to eliminate the deleterious effects of milling; Desai TR et al.; The effect of lyophilization and jet-milling on liposome integrity was investigated as a function of their ability to retain the encapsulated model drug on reconstitution of the dry products . The encapsulation efficiencies of the lyophilized and jet-milled formulations were determined at various concentrations of lactose . Lyophilization resulted in considerable leakage of the model drug at lower concentrations of lactose, and jet-milling further augmented the leakage for all the lyophilized formulations, with optimum retention obtained for formulations containing at least 10:1 molar ratio of lactose/lipid . In an attempt to overcome the deleterious effects of lyophilization and jet-milling, the feasibility of formulating phospholipid-based powders that result in spontaneous formation of liposomes in an aqueous environment has been investigated . Partitioning of three model drugs (viz., ciprofloxacin, CM3 peptide, and salbutamol sulfate) between the aqueous phase and spontaneously formed liposomes was determined in terms of encapsulation efficiency . The effects of several parameters, including lactose concentration, lipid composition, and lipid concentration on the encapsulation efficiency of these model drugs were investigated . The spontaneous formation of liposomes on dispersion of phospholipid-based powder formulations was further evidenced by freeze-fracture scanning electron microscopy . This novel approach for the delivery of liposomes in dry powder form appears promising because lyophilization is not involved and jet-milling of these powder formulations did not impact encapsulation efficiency . Jet-milled phospholipid-based powder formulations showed high encapsulation efficiencies of 96.2 +/- 1.4% for ciprofloxacin, 100% for CM3 peptide, and 45.3 +/- 3.1% for salbutamol sulfate compared with a high amount of leakage (> 50%) observed due to jet-milling of lyophilized liposome formulations encapsulating ciprofloxacin . J Urol, 2002 Mar, 167(3), 1288 - 94 Role of mitochondria in ciprofloxacin induced apoptosis in bladder cancer cells; Aranha O et al.; PURPOSE: In our earlier series we showed that ciprofloxacin inhibits bladder tumor cell growth with concomitant S/G2M cell cycle arrest and reported an increased Bax-to-Bcl-2 ratio in cells undergoing cell death . In the current series we elucidated the molecular mechanisms by which ciprofloxacin induces apoptotic processes . MATERIALS AND METHODS: Ciprofloxacin mediated mitochondrial depolarization was detected by flow cytometry in HTB9 cells . Mitochondrial permeability transition was measured by spectrophotometry in isolated mitochondria treated with ciprofloxacin in the presence and absence of cyclosporin . The consequential decrease in mitochondrial calcium, cytochrome c release and Bax translocation to mitochondria, which resulted in the activation of caspase 3 leading to apoptotic cell death, was measured by biochemical and confocal microscopy . RESULTS: Mitochondrial depolarization was observed during ciprofloxacin induced apoptotic processes . Cyclosporin A, a known inhibitor of the mitochondrial permeability transition pore, protected cells against decreased mitochondrial potential . Also, ciprofloxacin induced an alteration of mitochondrial calcium as early as 5 minutes and this disruption of intracellular calcium homeostasis was prevented by cyclosporin . Ciprofloxacin also had a direct effect on swelling of isolated mitochondria, which was absent in the presence of cyclosporin . Mitochondrial changes were accompanied by cytochrome c release and caspase 3 activation . Our findings also showed Bcl-2 dependent subcellular redistribution of Bax to the mitochondrial membrane in ciprofloxacin treated bladder tumor cells . CONCLUSIONS: The disruption of calcium homeostasis, mitochondrial swelling and redistribution of Bax to the mitochondrial membrane are key events in the initiation of apoptotic processes in ciprofloxacin treated bladder cancer cells. Expert Opin Investig Drugs, 2002 Feb, 11(2), 233 - 58 Fluoroquinolones and tuberculosis; Bryskier A et al.; Tuberculosis (TB) remains one of the main causes of morbidity worldwide, and the emergence of multi-drug resistant (MDR) Mycobacterium tuberculosis strains in some parts of the world has become a major concern . The decrease in activity of the major anti-TB drugs, such as isoniazid and rifampicin, is an important threat and alternative therapies are urgently required . The anti-TB activity of the fluoroquinolones has been under investigation since the 1980s . Many are active in vitro but only a few, including ofloxacin, ciprofloxacin, sparfloxacin, levofloxacin and lomefloxacin, have been clinically tested . Fluoroquinolones can be used in co-therapy with the available anti-TB drugs . However, the choice of fluoroquinolone should be based not only on the in vitro activity, but also on the long-term tolerance . Fluoroquinolones are novel anti-TB drugs to be used when a patient is infected with a MDR-TB strain. Eye, 2001 Dec, 15(Pt 6), 786 - 8 Scanning electron microscopic study of a Ciloxan bottle blocked by ciprofloxacin crystals; John T; PURPOSE: To report blockage of a commercially available ciprofloxacin bottle by white crystalline deposits . This study evaluated the ultrastructural features of the ciprofloxacin crystals . METHODS: A patient underwent intensive topical treatment of an infectious corneal ulcer with commercially available ciprofloxacin 0.3% ophthalmic solution . During treatment, the patient was unable to obtain medication from the ciprofloxacin bottle and required a new prescription . Examination of the bottle revealed that about 50% of the medication remained, but compression of the bottle with any amount of force failed to deliver any medication . On closer examination, a white material partially filled the nozzle track of the bottle and was on the outer bottle near the nozzle and the inner surface of the bottle cap . These white crystalline deposits were evaluated by scanning electron microscopy . RESULTS: Plate-like, needle, cable and spaghetti-like crystals were found . The needle crystals formed multiple petaloid patterns . CONCLUSIONS: This is the first report of blockage of a commercially available ciprofloxacin 0.3% bottle by ciprofloxacin crystals and the inability to deliver medication from the bottle . Ultrastructural study of the white crystalline deposits revealed four types of ciprofloxacin crystals. Cancer, 2002 Jan 1, 94(1), 97 - 103 A Phase II study of gemcitabine and docetaxel in patients with metastatic pancreatic carcinoma; Ryan DP et al.; BACKGROUND: Patients with metastatic pancreatic carcinoma have a poor survival . Chemotherapy with gemcitabine is the standard first-line treatment . In a Phase II trial at one academic cancer center, the clinical safety and activity of combining gemcitabine and docetaxel were assessed . METHODS: Patients with previously untreated, advanced pancreatic carcinoma were eligible . Bidimensionally measurable disease or evaluable disease with an elevated tumor marker, good performance status, and adequate organ function were required . Patients received docetaxel 60 mg/m(2) on Day 1 and gemcitabine 600 mg/m(2) on Days 1, 8, and 15 every 28 days . Ciprofloxacin was administered on Days 8-18 . Dose attenuations were made as indicated for toxicity . Patients were restaged radiographically after every two cycles . RESULTS: Thirty-four patients were enrolled, and 33 patients were evaluable for response . There were 23 men and 10 women among the evaluable patients . The median age was 63 years, and all patients had an Eastern Cooperative Oncology Group performance status of 0 or 1 . Three patients had received prior chemoradiation for postresection adjuvant therapy . One hundred forty-six cycles of chemotherapy were administered, and 5 cycles (3%) in 4 patients (12%) were complicated by febrile neutropenia . Twenty percent and 11% of patients on Day 8 and Day 15 doses of gemcitabine, respectively, were omitted for toxicity . The objective response rate was 18%, and the median survival was 8.9 months (95% confidence interval, 5.2-11.2 months) . The 1-year survival rate was 29% . CONCLUSIONS: The combination of gemcitabine and docetaxel in patients with advanced pancreatic carcinoma is well tolerated and is associated with moderate activity despite aggressive dose reduction . Whether combination regimens are more effective than single agents in the treatment of patients with pancreatic carcinoma awaits evaluation in randomized studies . J Infect Chemother, 2000 Sep, 6(3), 162 - 7 Comparative uptake of grepafloxacin and ciprofloxacin by a human monocytic cell line, THP-1; Hara T et al.; The present study was designed to compare the uptake of grepafloxacin by a human monocytic cell line, THP-1, with that of ciprofloxacin . THP-1 cells were incubated with 20 microg/ml of either drug, and the entry of the drugs into the cells was determined using a velocity gradient centrifugation technique and HPLC assay . Antibiotic uptake by the cells was expressed as the ratio of the intracellular to the extracellular drug concentration (IC/EC) . Grepafloxacin entered THP-1 cells readily within 5 min, and at steady-state (37 degrees C; 60 min), the IC/EC ratio of grepafloxacin (11.9 +/- 1.7; n = 13) was about 2.4-fold higher than that of ciprofloxacin (5.0 +/- 1.3; n = 13) . The ratios decreased at low incubation temperature (4 degrees C), in paraformaldehyde-treated dead cells, and at low extracellular pH (pH 6.0), but were not influenced by high extracellular pH (pH, 9.0) . Characterization of fluoroquinolone uptake suggests that these drugs penetrate the THP-1 membrane by passive diffusion, and also, in part, via an active transport system . We also examined the uptake of the two fluoroquinolones in phorbol 12 myristate 13-acetate (PMA)-stimulated adherent THP-1 cells (THP-1 macrophages) . The IC/EC ratios for both fluoroquinolones in the THP-1 macrophages were significantly higher than those in the THP-1 monocytes . Further the uptake of three other fluoroquinolones, levofloxacin, tosufloxacin, and sparfloxacin, by THP-1 monocytes was examined in comparative studies . The IC/EC ratio of grepafloxacin was comparable to that of sparfloxacin and significantly higher than that of the other fluoroquinolones . Our results indicate that grepafloxacin exhibits better intracellular accumulation than ciprofloxacin and other fluoroquinolones in human monocytic and macrophage-like cells. J Infect Chemother, 2000 Jun, 6(2), 72 - 6 Studies on the binding mechanism of fluoroquinolones to melanin; Fukuda M et al.; In order to elucidate the binding mechanism of melanin and fluoroquinolones (ofloxacin, norfloxacin, ciprofloxacin, lomefloxacin, levofloxacin), we investigated the interaction of fluoroquinolones with compounds such as l-beta-(3,4-dihydroxyphenyl) alanine (l-DOPA), l-tyrosine, 5-hydroxy-l-tryptophan, l-tryptophan, and l-phenylalanine, which possess the kind of functional groups that melanin does and are closely related to melanin . The recovery of drugs from the melanin-drug complexes by metal ions of Li, Na, Ka, Mg, Ca, Ba, Cu, Ni, and Fe was demonstrated . Smaller and highly charged cations were found to be more effective for this recovery, and magnesium ions were the most effective of all the ions investigated. J Infect Chemother, 2000 Mar, 6(1), 8 - 20 Prospects for development of new antimycobacterial drugs; Tomioka H; In this article, I have thoroughly reviewed the status of development of new antimycobacterial drugs, particularly fluoroquinolones (ciprofloxacin, ofloxacin, sparfloxacin, levofloxacin, gatifloxacin, sitafloxacin, and moxifloxacin), new macrolides (clarithromycin, azithromycin, and roxithromycin), rifamycin derivatives (rifabutin, rifapentine, and KRM-1648), and others . The main purpose of this review was to describe the in-vitro and in-vivo activities of these drugs against Mycobacterium tuberculosis and Mycobacterium avium complex . In addition, the therapeutic efficacy of these drugs in the clinical treatment of mycobacterial infections has also been briefly mentioned. Antimicrob Agents Chemother, 2002 Feb, 46(2), 385 - 91 Lack of effect of simultaneously administered didanosine encapsulated enteric bead formulation (Videx EC) on oral absorption of indinavir, ketoconazole, or ciprofloxacin; Damle BD et al.; Didanosine formulation that contains a buffer to prevent it from acid-mediated degradation can result in a significant decrease in the oral absorption of certain drugs because of interactions with antacids . An enteric formulation of didanosine is unlikely to cause such drug interactions because it lacks antacids . This study was undertaken to determine whether the enteric bead formulation of didanosine (Videx EC) influences the bioavailability of indinavir, ketoconazole, and ciprofloxacin, three drugs that are representative of a broader class of drugs affected by interaction with antacids . Healthy subjects of either gender were enrolled in three separate open-label, single-dose, two-way crossover studies . Subjects were randomized to treatment A (800 mg of indinavir, 200 mg of ketoconazole, or 750 mg of ciprofloxacin) or treatment B (same dose of indinavir, ketoconazole, or ciprofloxacin, but with 400 mg of didanosine as an encapsulated enteric bead formulation) . A lack of interaction was concluded if the 90% confidence interval (CI) of the ratio of the geometric means of log-transformed C(max) and AUC(0-infinity) values (i.e., values for the area under the concentration-time curve from time zero to infinity) of indinavir, ketoconazole, and ciprofloxacin were contained entirely between 0.75 and 1.33 . For indinavir (n = 23), the point estimate (90% CI; minimum, maximum) of the ratios of C(max) and AUC(0-infinity) values were 0.99 (0.91, 1.06) and 0.96 (0.91, 1.02), respectively . In the ketoconazole study, 3 of 24 subjects showed anomalous absorption of ketoconazole (i.e., an approximately 8-fold-lower AUC compared to historical data), which was the reference treatment . A post hoc analysis performed after these three subjects were excluded indicated that the point estimates (90% CI) of the ratios of C(max) and AUC(0-infinity) values were 0.99 (0.86, 1.14) and 0.97 (0.85, 1.10), respectively . For ciprofloxacin (n = 16), the point estimate (90% CI) of the ratios of C(max) and AUC(0-infinity) values were 0.92 (0.79, 1.07) and 0.91 (0.76, 1.08), respectively . All three studies clearly indicated a lack of interaction . The T(max) and t(1/2) for indinavir, ketoconazole, and ciprofloxacin were similar between treatments . Our results showed that the lack of interaction of didanosine encapsulated enteric bead formulation with indinavir, ketoconazole, and ciprofloxacin indicates that this enteric formulation of didanosine can be concomitantly administered with drugs whose bioavailability is known to be reduced by interaction with antacids. Ann Pharmacother, 2001 Dec, 35(12), 1540 - 7 Peripheral neuropathy associated with fluoroquinolones; Cohen JS; OBJECTIVE: To survey cases of fluoroquinolone-associated adverse events that included peripheral nervous system (PNS) symptoms posted on Internet Web sites . METHODS: Cases were obtained with the assistance of members of Web sites formed by people sustaining fluoroquinolone-related events . Information obtained met the standards of MedWatch, and each reported case was assessed using the Naranjo probability scale . RESULTS: In contrast to previous reports suggesting that fluoroquinolone-associated PNS events are mild and short-term, 36 of the 45 cases reported severe events that typically involved multiple organ systems . Although many newer cases are still evolving, symptoms had lasted more than three months in 71% of cases and more than one year in 58% . Onset of adverse events was usually rapid, with 15 (33%) events beginning within 24 hours of initiating treatment, 26 (58%) within 72 hours, and 38 (84%) within one week . Sixty courses of fluoroquinolones were prescribed: levofloxacin (n = 33 cases), ciprofloxacin (n = 11), ofloxacin (n = 6), lomefloxacin (n = 1), trovafloxacin (n = 1); in eight cases the same antibiotic was prescribed twice . CONCLUSIONS: These cases suggest a possible association between fluoroquinolone antibiotics and severe, long-term adverse effects involving the PNS as well as other organ systems . The severity of these cases may reflect a different population than typically reported to drug companies or MedWatch, which often originate from healthcare providers . In contrast, Internet Web sites may provide a forum for patients experiencing adverse effects that have not resolved promptly . Further study is warranted . Meanwhile the occurrence of PNS symptoms during fluoroquinolone therapy should prompt immediate discontinuation of the agent used. J Pharm Sci, 2002 Jan, 91(1), 196 - 205 A recirculatory model for local absorption and disposition of ciprofloxacin by measuring portal and systemic blood concentration difference; Moriwaki T et al.; A recirculatory model for the portal-systemic blood concentration difference (P-S difference) was developed to separately evaluate the rate and extent of absorption from the gastrointestinal tract into the portal system and disposition of a drug in the body . To apply this model to pharmacokinetic analysis, ciprofloxacin was selected as a model drug possessing a moderate intestinal absorption, and renal and hepatic elimination . The portal and systemic blood samples were simultaneously taken from rats at appropriate time points after intravenous and oral administration of ciprofloxacin at a dose of 5 mg/kg . After intravenous administration, little or no difference in the concentrations between the portal and systemic blood was observed, whereas after oral administration the concentrations of ciprofloxacin in the portal blood were consistently higher than those in the systemic blood over the time studied . This difference observed after oral administration is attributed to the absorption of ciprofloxacin from the gastrointestinal tract into the portal system . On the basis of the moment analysis deduced from the recirculatory model, the portal blood flow rate (Q(p)), the local absorption ratio from the gastrointestinal tract into the portal system (F(a)), the hepatic recovery ratio (F(h)), and bioavailability (BA) were then estimated . The obtained Q(p) of 2.81 L/h/kg, F(a) of 32.6, F(h) of 68.1, and BA of 22.2% were found to be in good agreement with the reported values . Furthermore, the mean local absorption time from the gastrointestinal tract into the portal system (t(a)) calculated by a nonlinear least-squares program {MULTI (FILT)} was almost identical with that by the global moments . These results suggest that the model proposed in this study would be useful for evaluating both in vivo absorption and disposition of drugs . Clin Experiment Ophthalmol, 2001 Dec, 29(6), 435 - 7 Delayed diffuse lamellar keratitis after laser in situ keratomileusis; Yeoh J et al.; Two cases are reported of delayed diffuse lamellar keratitis after uneventful laser in situ keratomileusis . The first patient presented with an epithelial defect 6 weeks after laser in situ keratomileusis . Three days later the defect was healed but diffuse lamellar keratitis was noted . This was treated with topical dexamethasone and ketorolac with complete resolution of the diffuse lamellar keratitis over 3 weeks . The second patient presented with an epithelial defect and gross diffuse lamellar keratitis 10 weeks after laser in situ keratomileusis . Treatment was with topical dexamethasone and ciprofloxacin with gradual resolution of the diffuse lamellar keratitis . Common to both patients was a background of rosacea, implanted debris with no initial reaction, and epithelial defects leading to diffuse lamellar keratitis . It is suggested that these two cases represent epithelial defect associated corneal infiltration, which resembles classical diffuse lamellar keratitis with the spread of inflammatory cells through a path of least resistance. J R Coll Surg Edinb, 2001 Dec, 46(6), 334 - 7 Pouchitis following restorative proctocolectomy for ulcerative colitis: incidence and therapeutic outcome; Madiba TE et al.; BACKGROUND: Pouchitis is a significant sequel of restorative proctocolectomy . This study was undertaken to document the incidence of pouchitis at the Edinburgh Royal Infirmary and to assess outcome of treatment with metronidazole . METHODS: Patients who developed pouchitis following restorative proctocolectomy for ulcerative colitis form the basis of this study . Pouchitis was suspected if patients developed diarrhoea with or without blood, mucus or pus . Diagnosis was confirmed with pouch endoscopy and biopsy . RESULTS: From 1990 to 1999 (10 years) 139 patients underwent restorative proctocolectomy and ileo-anal pouch anastomosis (135 J pouches and 4 W pouches) . Their median age was 35 years (range 13-74) . There were 68 females and 71 males . The indication for operation was failed medical treatment in 104 patients and toxic megacolon in 35 . Forty-seven patients (34%) developed pouchitis (21 females and 26 males) . Symptoms were diarrhoea (35), diarrhoea, mucus and pus (5) and diarrhoea and blood (7) . Symptoms of pouchitis started at an average of 33.51 + 29.2 months (range 2-102, median 18) . All patients were treated with metronidazole for a minimum of one month . Thirty-six patients (77%) resolved on metronidazole alone . Nine patients (19%) went on to develop chronicity and were managed by long-term metronidazole (and/or ciprofloxacin) . A further 2 patients (4%) had treatment resistant pouchitis and required pouch excision . CONCLUSION: Pouchitis is common following restorative proctocolectomy for ulcerative colitis . Treatment with metronidazole is associated with improvement in the majority of cases . In patients with chronic pouchitis maintenance of remission is possible with antibiotics . A high index of suspicion is advocated in patients who develop severe diarrhoea following this procedure. Pharmacotherapy, 2001 Dec, 21(12), 1468 - 72 Rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin; Frothingham R; STUDY OBJECTIVE: To compare the rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin administration . DESIGN: Retrospective database analysis . INTERVENTION: Evaluation of reported rates of torsades de pointes in patients who received these quinolones between January 1, 1996, and May 2, 2001 . MEASUREMENTS AND MAIN RESULTS: In the United States, 25 cases of torsades de pointes associated with these quinolones (ciprofloxacin 2, ofloxacin 2, levofloxacin 13, gatifloxacin 8, moxifloxacin 0) were identified . Ciprofloxacin was associated with a significantly lower rate of torsades de pointes (0.3 cases/10 million prescriptions, 95% confidence interval {CI} 0.0-1.1) than levofloxacin (5.4/10 million, 95% CI 2.9-9.3, p<0.001) or gatifloxacin (27/10 million, 95% CI 12-53, p<0.001 for comparison with ciprofloxacin or levofloxacin) . When the analysis was limited to the first 16 months after initial U.S . approval of the agent, the rates for levofloxacin (16/10 million) and gatifloxacin (27/10 million) were similar (p>0.5) . CONCLUSION: Levofloxacin should be administered with caution in patients with risk factors for QT prolongation . Gatifloxacin should be avoided in the same patient population, and the recommended dosage of 400 mg/day should not be exceeded. J Chemother, 2001 Oct, 13(5), 563 - 8 Effects of repeated rifabutin administration on the pharmacokinetics of intravenous and oral ciprofloxacin in mice; Liu XG et al.; The combination of rifabutin and ciprofloxacin is potentially useful for the treatment of disseminated Mycobacterium avium-intracellulare (MAC) diseases in HIV-infected patients . Rifabutin is a metabolic enzyme inducer structurally similar to its predecessor, rifampin . Using a mouse model, the effects of repeated exposure of rifabutin on the pharmacokinetics of ciprofloxacin after intravenous (i.v.) and oral (p.o.) dosing were investigated in the present study . Results showed that repeated exposure of rifabutin, relative to control, caused a 16% increase in the plasma clearance (CL) of ciprofloxacin after i.v . dosing (4.19 vs . 4.87 L/h/kg) . Estimates of elimination half-life (T1/2) were not affected by rifabutin (control: 0.81 vs . rifabutin pretreated: 1.18 h) . The data obtained after oral dosing showed that repeated rifabutin dosing caused a significant reduction in the maximal plasma concentration (Cmax: 1.34 vs . 0.91 microg/mL) and a longer time to Cmax (Tmax: 0.17 vs . 0.33 h) . These changes might be in part attributable to the increase in oral clearance (CL/F) by 18% . With or without rifabutin pretreatment, the T1/2 estimates of ciprofloxacin for p.o . dosing were similar (2.37-2.58 h) and were approximately twice as long as those obtained after i.v . dosing . Since the changes in systemic exposure as a result of rifabutin pretreatment were similar after i.v . and p.o . dosing, the oral bioavailability (F) of ciprofloxacin remained unaffected by rifabutin at approximately 38% . The effects of rifabutin on the pharmacokinetics of ciprofloxacin appear to be moderate in the mouse model which might be attributable to the absorption and distribution behavior of the quinolone antibiotic . The therapeutic implications of this interaction, if any, remain to be defined. J Antimicrob Chemother, 2002 Jan, 49(1), 55 - 9 Molecular epidemiology and evolution of resistance to quinolones in Escherichia coli after prolonged administration of ciprofloxacin in patients with prostatitis; Horcajada JP et al.; The emergence and evolution of quinolone-resistant Escherichia coli in faeces of patients with prostatitis treated with high-dose oral ciprofloxacin for 1 month were studied . In 11 of 23 patients, from whom only quinolone-susceptible E . coli was isolated before treatment, quinolone-resistant strains, genetically distinct from the quinolone-susceptible ones, predominated during and just after therapy . Two months after treatment, these were completely displaced by quinolone-susceptible E . coli, genetically distinct from the E . coli isolated before and during therapy . Hence, during ciprofloxacin therapy, half of the patients were transiently colonized with new, quinolone-resistant strains of E . coli. Vet J, 2002 Jan, 163(1), 85 - 93 Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in goats given enrofloxacin alone and in combination with probenecid; Rao GS et al.; The pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were investigated in goats given enrofloxacin alone or in combination with probenecid . Enrofloxacin was administered i.m . at a dosage of 5 mg x kg(-1) alone or in conjunction with probenecid (40 mg x kg(-1), i.v.) . Blood samples were drawn from the jugular vein at predetermined time intervals after drug injection . Plasma was separated and analysed simultaneously for enrofloxacin and ciprofloxacin by reverse-phase high performance liquid chromatography . The plasma concentration-time data for both enrofloxacin and ciprofloxacin were best described by a one-compartment open pharmacokinetic model . The elimination half-life (t(1/2beta)), area under the plasma concentration-time curve (AUC), volume of distribution (V(d(area))), mean residence time (MRT) and total systemic clearance (Cl(B)) were 1.39 h, 7.82 microg x h x mL, 1.52 L x kg(-1), 2.37 h and 802.9 mL x h(-1) x kg(-1), respectively . Enrofloxacin was metabolized to ciprofloxacin in goats and the ratio between the AUCs of ciprofloxacin and enrofloxacin was 0.34 . The t(1/2beta), AUC and MRT of ciprofloxacin were 1.82 h, 2.55 microg x h x mL and 3.59 h, respectively . Following combined administration of probenecid and enrofloxacin in goats, the sum of concentrations of enrofloxacin and ciprofloxacin levels > or = 0.1 microg x mL(-1) persisted in plasma up to 12 h.Co-administration of probenecid did not affect the t(1/2beta), AUC, V(d (area)) and Cl(B) of enrofloxacin, whereas the values of t(1/2beta) (3.85 h), AUC (6.29 microg x h x mL), MRT (7.34 h) and metabolite ratio (0.86) of ciprofloxacin were significantly increased . The sum of both enrofloxacin and ciprofloxacin levels was > or = 0.1 microg x mL(-1) and was maintained in plasma up to 8 h in goats after i.m . administration of enrofloxacin alone . These data indicate that a 12 h dosing regime may be appropriate for use in goats . Cancer, 2001 Nov 15, 92(10), 2508 - 16 High-dose mitoxantrone and cyclophosphamide without stem cell support in patients with high-risk and advanced breast carcinoma: a Phase II multicentric trial; Perez-Gracia JL et al.; BACKGROUND: Currently employed high-dose regimens for patients with breast carcinoma consist mainly of single-cycle combinations of alkylating agents . In a previous Phase I trial, the authors developed a tandem high-dose combination of two cycles of mitoxantrone and cyclophosphamide for the treatment of patients with metastatic breast carcinoma (MBC) and high-risk breast carcinoma (HRBC) . Treatment was delivered with granulocyte-colony stimulating factor (G-CSF) but without stem cell support to avoid potential tumor cell reinfusion . The objective was to validate the safety and obtain preliminary efficacy assessment of this combination in a Phase II trial . METHODS: Fifty-three patients were included: 27 patients with MBC and 26 patients with HRBC . After standard induction treatment, patients received two cycles of mitoxantrone 25 mg/m2 and cyclophosphamide 4000 mg/m2 separated by a 4-week interval . Patients received G-CSF and ciprofloxacin until hematologic recovery . Follow-up was performed in an outpatient setting . RESULTS: One hundred one of 106 projected cycles (95%) were delivered . The mean dose intensities achieved were mitoxantrone 5.8 mg/m2 per week and cyclophosphamide 933 mg/m2 per week . Infection developed in 46% of the cycles, and platelet transfusions were required in 42% . Nonhematologic toxicity was mainly Grade 3 emesis . There were no toxic deaths . In 17 evaluable patients with MBC, 13 patients (77%) had response improvements, including 7 complete responses (41%) . CONCLUSIONS: Treatment with two cycles of mitoxantrone 25 mg/m2 and cyclophosphamide 4000 mg/m2 with G-CSF but without stem cell support was well tolerated . The dose intensities achieved approach those obtained with conventional high-dose therapy . This combination warrants further investigation as an alternative to conventional high-dose regimens . J Cataract Refract Surg, 2001 Dec, 27(12), 1975 - 8 Topical ciprofloxacin-dexamethasone combination therapy after cataract surgery: randomized controlled clinical trial; Mohan N et al.; PURPOSE: To determine the efficacy of a combination of ciprofloxacin 0.3% and dexamethasone 0.1% eyedrops in controlling immediate inflammation after cataract surgery . SETTING: Dr . Rajendra Prasad Centre for Ophthalmic Sciences and Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India . METHODS: This randomized controlled clinical trial comprised 61 patients, 31 of whom were treated with a combined ciprofloxacin-dexamethasone suspension (study group) and 30, with a standard formulation of betamethasone and neomycin eyedrops (control group) . One and 7 days postoperatively, pain, lid edema, lacrimation, conjunctival congestion, aqueous flare and cells, and side effects were noted . A conjunctival swab for bacteria and a fungus culture were sent for evaluation 7 days postoperatively . RESULTS: At 7 days, there was no statistically significant difference between groups in lid edema, conjunctival congestion, anterior segment inflammation, lacrimation, or pain . Two patients in the ciprofloxacin-dexamethasone group noted white deposits in and around the eye that resolved after the dose was reduced to 4 times a day . No patient reported or developed an allergic reaction to either drug combination . CONCLUSION: A ciprofloxacin-dexamethasone combination was effective in controlling inflammation after cataract surgery. Drug Saf, 2001, 24(13), 947 - 59 Therapeutic drug monitoring databases for postmarketing surveillance of drug-drug interactions; Gex-Fabry M et al.; Drug-drug interactions can be associated with patient morbidity due to either increased toxicity or a potentially ineffective concentration . Because interactions cannot always be anticipated during drug development and actual patients receiving a drug for therapeutic use often differ from those included in clinical trials, postmarketing surveillance is essential . Therapeutic drug monitoring (TDM) databases offer a unique opportunity in this respect . Prerequisites for TDM databases to provide valid information in a pharmacoepidemiological perspective include the following: precise description of exposure to the potentially interacting drugs; measurement of parent compound and active metabolites through accurate and precise analytical techniques; documentation of relevant patient characteristics that may act as confounding factors (e.g . gender, age, smoking habits); repeated assessments over time if possible; and sound pharmacokinetic framework for data selection, analysis and interpretation . The contribution of TDM to the documentation of drug-drug interactions takes advantage of different possible study designs, discussed on the basis of recently published studies . The single case report plays an important role as an alert signal . It is illustrated for a patient on long-term treatment, who displayed an unexpectedly high clozapine concentration after the introduction of ciprofloxacin comedication . The prospective on and off comedication panel study shows advantages in terms of carefully selected inclusion criteria and control of treatment modalities . A study of the thioridazine-fluvoxamine interaction is presented, with patients followed on thioridazine monotherapy, after introduction of fluvoxamine and after its discontinuation . The main advantage of the retrospective large-scale TDM database screen is representativeness of patients actually treated, whereas drawbacks are related to quality of data and suitability for valid interpretation . Such an approach is illustrated by a review of data collected over 10 years of routine TDM that allowed documenting induction of nortriptyline metabolism by carbamazepine and inhibition by several phenothiazines . Finally, population pharmacokinetics is well suited to observational data collected for TDM purpose, provided quality is ascertained . Focus is placed on interindividual variability and relationship between pharmacokinetic parameters and patient characteristics, including comedication . The population approach is discussed with respect to a study that documented a 32% increase of haloperidol clearance associated with anticonvulsant comedication, in addition to effects of age and bodyweight . Among factors to consider for improved effectiveness in the use of TDM databases for postmarketing surveillance of drug-drug interactions, integration of efficacy and safety data in future studies and communication of expert recommendations to prescribing physicians are essential. J Antimicrob Chemother, 2001 Dec, 48(6), 787 - 91 Accumulation of five fluoroquinolones by Mycobacterium tuberculosis H37Rv; Piddock LJ et al.; The accumulation of ciprofloxacin, norfloxacin, moxifloxacin, levofloxacin and ofloxacin by Mycobacterium tuberculosis H37Rv was determined with a modified fluorescence method . The time to achieve a steady-state concentration (SSC) of each agent in M . tuberculosis was 60-240 s . Moxifloxacin was accumulated to the lowest concentration and ciprofloxacin to the highest . However, ciprofloxacin took longer to achieve an SSC than the other four agents; levofloxacin reached steady state in the shortest time . Larger fluoroquinolones accumulated to the lowest concentration and more slowly . Although all five agents had low hydrophobicity values (P(app) < or =0.11), those with the lowest values accumulated to the higher concentrations. J Eur Acad Dermatol Venereol, 2001 Jul, 15(4), 334 - 6 Acral necrosis by Stenotrophomonas maltophilia; Pereira O et al.; BACKGROUND: Stenotrophomonas maltophilia (SM) has been considered a nosocomial pathogen . Nevertheless, community acquired infection may occur more frequently than usually recognized . CASE: We describe distal necrosis of the fingers by SM in a farmer, contracted in the community and successfully treated with a combination of cotrimoxazole and ciprofloxacin . The patient was diagnosed with chronic lymphocytic leukaemia 6 months later . CONCLUSIONS: This unusual presentation shows that infection with SM should be included in the differential diagnosis of the skin and soft tissue infection, even in apparently healthy patients. Dtsch Tierarztl Wochenschr, 2001 Oct, 108(10), 429 - 34 Disposition kinetics of danofloxacin and ciprofloxacin in broiler chickens; el-Gendi AY et al.; Disposition kinetics of danofloxacin and ciprofloxacin were studied in broiler chickens following intravenous, intramuscular and oral administration in a single dose of 5 and 10 mg/kg-1 body weight respectively . In addition, tissue distribution and residual pattern of both drugs were determined . The maximum serum concentration (Cmax) after intramuscular and oral administration were 1.03 and 0.55 mu/ml for danofloxacin and 2.92 and 1.24 mu/ml for ciprofloxacin attained at 0.8 and 2.43 and 0.55 and 1.27 hours for danofloxacin and ciprofloxacin respectively . The volume of distribution and systemic bioavailability were higher for danofloxacin (Vdss 2.21 L/kg and F% 96.56 and 81.4%) as compared with ciprofloxacin (Vdss 1.41 L/kg and F% 75.5 and 29.4%) . Data relating to intravenous injection for both drugs were analyzed using a two compartment open model curve fit . Danofloxacin and ciprofloxacin were not detected in the serum of broilers at the 5th and 3rd day respectively following the drugs withdrawal while were detected in liver, kidneys, spleen and lungs . Danofloxacin completely disappeared from all tissues at the 13th day after stopping of the drug medication but ciprofloxacin disappeared after 5 days only. Inflamm Bowel Dis, 2001 Nov, 7(4), 301 - 5 A randomized clinical trial of ciprofloxacin and metronidazole to treat acute pouchitis; Shen B et al.; Metronidazole is effective for the treatment of acute pouchitis after ileal pouch-anal anastomosis, but it has not been directly compared with other antibiotics . This randomized clinical trial was designed to compare the effectiveness and side effects of ciprofloxacin and metronidazole for treating acute pouchitis . Acute pouchitis was defined as a score of 7 or higher on the 18-point Pouchitis Disease Activity Index (PDAI) and symptom duration of 4 weeks or less . Sixteen patients were randomized to a 2-week course of ciprofloxacin 1,000 mg/d (n = 7) or metronidazole 20 mg/kg/d (n = 9) . Clinical symptoms, endoscopic findings, and histologic features were assessed before and after therapy . Both ciprofloxacin and metronidazole produced a significant reduction in the total PDAI score as well as in the symptom, endoscopy, and histology subscores . Ciprofloxacin lowered the PDAI score from 10.1+/-2.3 to 3.3+/-1.7 (p = 0.0001), whereas metronidazole reduced the PDAI score from 9.7+/-2.3 to 5.8+/-1.7 (p = 0.0002) . There was a significantly greater reduction in the ciprofloxacin group than in the metronidazole group in terms of the total PDAI (6.9+/-1.2 versus 3.8+/-1.7; p = 0.002), symptom score (2.4+/-0.9 versus 1.3+/-0.9; p = 0.03), and endoscopic score (3.6+/-1.3 versus 1.9+/-1.5; p = 0.03) . None of patients in the ciprofloxacin group experienced adverse effects, whereas three patients in the metronidazole group (33%) developed vomiting, dysgeusia, or transient peripheral neuropathy . Both ciprofloxacin and metronidazole are effective in treating acute pouchitis with significant reduction of the PDAI scores . Ciprofloxacin produces a greater reduction in the PDAI and a greater improvement in symptom and endoscopy scores, and is better tolerated than metronidazole . Ciprofloxacin should be considered as one of the first-line therapies for acute pouchitis. Antimicrob Agents Chemother, 2001 Dec, 45(12), 3387 - 92 Intrinsic resistance of Mycobacterium smegmatis to fluoroquinolones may be influenced by new pentapeptide protein MfpA; Montero C et al.; The fluoroquinolones (FQ) are used in the treatment of Mycobacterium tuberculosis, but the development of resistance could limit their effectiveness . FQ resistance (FQ(R)) is a multistep process involving alterations in the type II topoisomerases and perhaps in the regulation of efflux pumps, but several of the steps remain unidentified . Recombinant plasmid pGADIV was selected from a genomic library of wild-type (WT), FQ-sensitive M . smegmatis by its ability to confer low-level resistance to sparfloxacin (SPX) . In WT M . smegmatis, pGADIV increased the MICs of ciprofloxacin (CIP) by fourfold and of SPX by eightfold, and in M . bovis BCG it increased the MICs of both CIP and SPX by fourfold . It had no effect on the accumulation of (14)C-labeled CIP or SPX . The open reading frame responsible for the increase in FQ(R), mfpA, encodes a putative protein belonging to the family of pentapeptides, in which almost every fifth amino acid is either leucine or phenylalanine . Very similar proteins are also present in M . tuberculosis and M . avium . The MICs of CIP and SPX were lower for an M . smegmatis mutant strain lacking an intact mfpA gene than for the WT strain, suggesting that, by some unknown mechanism, the gene product plays a role in determining the innate level of FQ(R) in M . smegmatis. Clin Pharmacokinet, 2001, 40(10), 723 - 51 Pharmacokinetic considerations in the treatment of inflammatory bowel disease; Schwab M et al.; This review describes the pharmacokinetics of the major drugs used for the treatment of inflammatory bowel disease . This information can be helpful for the selection of a particular agent and offers guidance for effective and well tolerated regimens . The corticosteroids have a short elimination half-life (t1/2beta) of 1.5 to 4 hours, but their biological half-lives are much longer (12 to 36 hours) . Most are moderate or high clearance drugs that are hepatically eliminated, primarily by cytochrome P450 (CYP) 3A4-mediated metabolism . Prednisone and budesonide undergo presystemic elimination . Any disease state or comedication affecting CYP3A4 activity should be taken into account when prescribing corticosteroids . Depending on the preparation used, 10 to 50% of an oral or rectal dose of mesalazine is absorbed . Rapid acetylation in the intestinal wall and liver (t1/2beta 0.5 to 2 hours) and transport probably by P-glycoprotein affect mucosal concentrations of mesalazine, which apparently determine clinical response . Any clinical condition influencing the release and topical availability of mesalazine might modify its therapeutic potential . Metronidazole has high (approximately 90%) oral bioavailability, with hepatic elimination characterised by a t1/2beta of 6 to 10 hours and a total clearance of about 4 L/h/kg . Ciprofloxacin is largely excreted unchanged both renally (about 45% of dose) and extrarenally (25%), with a relatively short t1/2beta (3.5 to 7 hours) . Thus, renal function affects the systemic availability of ciprofloxacin . Both mercaptopurine and its prodrug azathioprine are metabolised to active compounds (6-thioguanine nucleotides; 6-TGN) by hypoxanthine-guanine phosphoribosyltransferase and to inactive metabolites by the polymorphically expressed thiopurine S-methyltransferase (TPMT) and xanthine oxidase . Patients with low TPMT activity have a higher risk of developing haemopoietic toxicity . Both mercaptopurine and azathioprine have a short t1/2beta (1 to 2 hours), but the t1/2beta of 6-TGN ranges from 3 to 13 days . Therapeutic response seems to be related to 6-TGN concentration . Almost complete bioavailability has been observed after intramuscular and subcutaneous administration of methotrexate, which is predominantly (85%) excreted as unchanged drug with a t1/2beta of up to 50 hours . Thus, renal function is the major determinant for disposition of methotrexate . Cyclosporin is slowly and incompletely absorbed . It is extensively metabolised by CYP3A4/5 in the liver and intestine (median t1/2beta and clearance 7.9 hours and 0.46 L/h/kg, respectively), and inhibitors and inducers of CYP3A4 can modify response and toxicity . Infliximab is predominantly distributed to the vascular compartment and eliminated with a t1/2beta between 10 and 14 days . No accumulation was observed when it was administered at intervals of 4 or 8 weeks . Methotrexate may reduce the clearance of infliximab from serum. Am J Ophthalmol, 2001 Nov, 132(5), 788 - 90 Endophthalmitis caused by Moraxella species; Berrocal AM et al.; PURPOSE: To report the incidence, clinical presentation, antibiotic sensitivities, and treatment outcomes for endophthalmitis caused by Moraxella species . METHODS: Consecutive interventional case series . Medical records were reviewed of all patients treated at Bascom Palmer Eye Institute between 1991 and 2000 for endophthalmitis caused by Moraxella species . RESULTS: Moraxella species were recovered from 9 patients (10 eyes), or 1.3% (10 of 757) of all culture-proven bacterial endophthalmitis cases; Moraxella catarrhalis was recovered from 7 eyes and Moraxella osloensis from 3 . Endophthalmitis was delayed-onset (5 months to 10 years postoperatively) and bleb-associated in 9 eyes and t