Pharmacokinetics Of Ciprofloxacin Research Articles

Single and Multiple Pharmacokinetics of Enrofloxacin and Ciprofloxacin in Pigs

Pharmacokinetics of Enrofloxacin (ENR) and Ciprofloxacin (CPX) in pig plasma was studied by HPLC-FL analysis using two injectable solutions, Enromic ® 20% (single dose of 7.5 mg ENR Kg -1 body weight) and Enromic ® 10% (multiple dose of 2.5 mg ENR Kg -1 body weight/day during 3 consecutive days). For the method validation, standard calibration curves were prepared between 0.025 and 0.5 μg mL -1 , with r 2 >0.9998 for both analytes. Quantification limits were 0.0282 and 0.0289 μg mL -1 for ENR y CPX, respectively; recovery percentages vary between 90.09% and 104.84% for ENR, and 63.01% and 89.01% for CPX, and precision obtained for measurements made on different days, expressed as %RSD, varied between 2.70% and 15.26% for ENR, and between 6.58% and 13.31% for CPX. Pharmacokinetic parameters gave values for Enromic ® 20% of 1.139 ± 0.320 μg mL -1 (C max ), 3.500 ± 1.581 h (T max ) and 17.821 ± 3.020 μg mL -1 h (AUC 0→∞ ) DU for ENR and 0.047 ± 0.010 μg mL -1 (C max ), 9.200 ± 1.932 h (T max ) and 1.027 ± 0.138 μg mL -1 h (AUC 0→∞ ) for CPX . For the product Enromic ® 10% (multiple doses), values were 0.428 ± 0.119 μg mL -1 (C max ), 5.000 ± 0 h (T max ) and 4.616 ± 1.138 μg mL -1 h (AUC 0→∞ ) for ENR and for CPX were 0.023 ± 0.006 μg mL -1 (C max ), 6.000 ± 2.108 h (T max ) and 0.424 ± 0.129 μg mL -1 h (AUC 0→∞ ) . We conclude that the most analyzed parameters are similar for both products, regardless of their different administration regime.

Ciprofloxacin pharmacokinetics and oral absorption of generic ciprofloxacin tablets in dogs

To determine the pharmacokinetics of ciprofloxacin in dogs, including oral absorption following administration of generic ciprofloxacin tablets. 6 healthy Beagles. In a crossover study design, ciprofloxacin was administered as a generic tablet (250 mg, PO; mean dose, 23 mg/kg) and solution (10 mg/kg, IV) to 6 dogs. In a separate experiment, 4 of the dogs received ciprofloxacin solution (10 mg/mL) PO via stomach tube (total dose, 250 mg). Blood samples were collected before (time 0) and for 24 hours after each dose. Plasma concentrations were analyzed with high-pressure liquid chromatography. Pharmacokinetic analysis was performed by means of compartmental modeling. When ciprofloxacin was administered as tablets PO, peak plasma concentration was 4.4 μg/mL (coefficient of variation [CV], 55.9%), terminal half-life (t(1/2)) was 2.6 hours (CV, 10.8%), area under the time-concentration curve was 22.5 μg•h/mL (CV, 62.3%), and systemic absorption was 58.4% (CV, 45.4%). For the dose administered IV, t(1/2) was 3.7 hours (CV, 52.3%), clearance was 0.588 L/kg/h (CV, 33.9%), and volume of distribution was 2.39 L/kg (CV, 23.7%). After PO administration as a solution versus IV administration, plasma concentrations were more uniform and consistent among dogs, with absorption of 71% (CV, 7.3%), t(1/2) of 3.1 hours (CV, 18.6%), and peak plasma concentration of 4.67 μg/mL (CV, 17.6%). Inconsistent oral absorption of ciprofloxacin in some dogs may be formulation dependent and affected by tablet dissolution in the small intestine. Because of the wide range in oral absorption of tablets, the dose needed to reach the pharmacokinetic-pharmacodynamic target concentration in this study ranged from 12 to 52 mg/kg (CV, 102%), with a mean dose of 25 mg/kg, once daily, for bacteria with a minimum inhibitory concentration ≤ 0.25 μg/mL.

Drug-drug interaction between ciprofloxacin and diclofenac ophthalmic drops at ocular level

In present times, there has been interest in multi-drug combinations for treatment of ocular infections, which are more commonly antibiotics and analgesics. Ciprofloxacin and diclofenac sodium were used concomitantly and pharmacokinetic drug-drug interactions between them were studied. To investigate disposition kinetics of ciprofloxacin eye drops (0.3%) alone and with co-administration of diclofenac sodium eye drops (0.1%) for pharmacokinetic drug-drug interaction(s). A randomized clinical trial was conducted in 84 human volunteers and the aqueous humor samples were collected from the eyes at various time intervals and concentration of ciprofloxacin in aqueous humor was determined using a validated reversed-phase high performance liquid-chromatography/ultraviolet detection method. The results were subjected to statistical analysis to determine whether a statistically significant difference was observed between the two groups. The mean age of the patients in this study ranged from 40 to 83 years, and gender distribution was 46.0% female and 54.0% males. The maximum concentration of ciprofloxacin in aqueous humor observed was 0.47 ± 0.057 µg/ml at 0.83 h. While the maximum concentration with concurrent administration of ciprofloxacin with diclofenac sodium was 0.44 ± 0.00577 µg/ml at 0.25 h. Time to reach maximum concentration was decreased to 0.3 h. t1/2abs and tα1/2 were not significantly affected by co-administration of the ciprofloxacin eye drops with the diclofenac sodium eye drops (P = 0.73), however, t1/2βwas significantly affected (P = 0.036). Similarly, apparent volume of distribution, volume of central compartment, steady-state distribution volume, AUC0-t and MRT were also significantly reduced due to concurrent administration of the diclofenac sodium eye drops with the ciprofloxacin eye drops (P = 0.021, 0.0.017, 0.05, 0.01 and 0.04). On the other hand, the ocular Clt was significantly elevated (P = 0.04), while absorption rate constant (P = 0.58) was non significantly decreased due to concurrent administration of the diclofenac sodium eye drops, while Cmax was not significantly affected. Diclofenac sodium affects the pharmacokinetics of ciprofloxacin when co-administered with ciprofloxacin eye drops. Key words: Ciprofloxacin ophthalmic drops, pharmacokinetics drug-drug interaction, aqueous humor.

Administration of Ciprofloxacin and Capsaicin in Rats to Achieve Higher Maximal Serum Concentrations

To test if capsaicin could improve the bioavailability of ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, CAS 85721-33-1, Bay q 3939) in rats, 0.01, 0.1, 0.5 and 1% capsaicin ((E)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methyl-6-nonenamide, trans-8-methyl-N-vanillyl-6-nonenamide, CAS 404-86-4) dissolved in ethanol and mixed with 20 mg/kg of ciprofloxacin were orally administered to groups of 10 rats each. Control groups were dosed with capsaicin-free, ethanol-containing or ethanol-free ciprofloxacin. Reference intravenous pharmacokinetics of ciprofloxacin was also established. The results revealed that capsaicin increased ciprofloxacin bioavailability by approximately 70% in groups receiving preparations containing capsaicin at a rate of 0.01, 0.1 and 0.5%. Higher concentrations failed to further increase bioavailability. However, capsaicin appears to have little or no impact on the rate of absorption or clearance of ciprofloxacin. Considering that 0.01% or 0.1% capsaicin are unlikely to upset the gastrointestinal tract, it may be worth attempting to study if a similar effect occurs in man, and to evaluate if the addition of capsaicin can be used as a method to increase the area under the curve/minimum inhibitory concentration rate, a key variable to improve clinical efficacy of ciprofloxacin.

An evaluation of ciprofloxacin pharmacokinetics in critically ill patients undergoing continuous veno-venous haemodiafiltration

BackgroundThe study aimed to investigate the pharmacokinetics of intravenous ciprofloxacin and the adequacy of 400 mg every 12 hours in critically ill Intensive Care Unit (ICU) patients on continuous veno-venous haemodiafiltration (CVVHDF) with particular reference to the effect of achieved flow rates on drug clearance.MethodsThis was an open prospective study conducted in the intensive care unit and research unit of a university teaching hospital. The study population was seven critically ill patients with sepsis requiring CVVHDF.Blood and ultrafiltrate samples were collected and assayed for ciprofloxacin by High Performance Liquid Chromatography (HPLC) to calculate the model independent pharmacokinetic parameters; total body clearance (TBC), half-life (t1/2) and volume of distribution (Vd). CVVHDF was performed at prescribed dialysate rates of 1 or 2 L/hr and ultrafiltration rate of 2 L/hr. The blood flow rate was 200 ml/min, achieved using a Gambro blood pump and Hospal AN69HF haemofilter.ResultsSeventeen profiles were obtained. CVVHDF resulted in a median ciprofloxacin t1/2 of 13.8 (range 5.15-39.4) hr, median TBC of 9.90 (range 3.10-13.2) L/hr, a median Vdss of 125 (range 79.5-554) L, a CVVHDF clearance of 2.47+/-0.29 L/hr and a clearance of creatinine (Clcr) of 2.66+/-0.25 L/hr. Thus CVVHDF, at an average flow rate of ~3.5 L/hr, was responsible for removing 26% of ciprofloxacin cleared. At the dose rate of 400 mg every 12 hr, the median estimated Cpmax/MIC and AUC0-24/MIC ratios were 10.3 and 161 respectively (for a MIC of 0.5 mg/L) and exceed the proposed criteria of >10 for Cpmax/MIC and > 100 for AUC0-24/MIC. There was a suggestion towards increased ciprofloxacin clearance by CVVHDF with increasing effluent flow rate.ConclusionsGiven the growing microbial resistance to ciprofloxacin our results suggest that a dose rate of 400 mg every 12 hr, may be necessary to achieve the desired pharmacokinetic - pharmacodynamic (PK-PD) goals in patients on CVVHDF, however an extended interval may be required if there is concomitant hepatic impairment. A correlation between ciprofloxacin clearance due to CVVHDF and creatinine clearance by the filter was observed (r2 = 0.76), providing a useful clinical surrogate marker for ciprofloxacin clearance within the range studied.Trial RegistrationCurrent Controlled Trials ISRCTN52722850

Pharmacokinetics of Ciprofloxacin and Its Penetration into Bronchial Secretions of Mechanically Ventilated Patients with Chronic Obstructive Pulmonary Disease

We evaluated the pharmacokinetic profile of ciprofloxacin and its penetration into bronchial secretions of critically ill patients with chronic obstructive pulmonary disease (COPD). Twenty-five mechanically ventilated patients with severe COPD who were suffering from an acute, infectious exacerbation were included in this prospective, open-label study. All subjects received a 1-hour intravenous infusion of 400 mg ciprofloxacin every 8 h. Serial blood and bronchial secretion samples were obtained at steady state, and concentrations were determined using high-performance liquid chromatography. The pharmacodynamic parameters that are associated with the efficacy of fluoroquinolones against Gram-negative pathogens were also calculated. The mean peak (maximum) concentration (C(max)) and trough (minimum) concentration in plasma were 5.37 ± 1.57 and 1 ± 0.53 mg/liter, respectively. Mean values for volume of distribution, clearance, half-life, and area under the curve from 0 to 24 h (AUC(0-24)) were 169.87 ± 84.11 liters, 26.96 ± 8.86 liters/h, 5.35 ± 2.21 h, and 47.41 ± 17.02 mg · h/liter, respectively. In bronchial secretions, a mean C(max) of 3.08 ± 1.21 mg/liter was achieved in 3.12 ± 1.01 h, and the penetration ratio was 1.16 ± 0.59. The target of AUC(0-24)/MIC of ≥125 was attained in all patients, in the majority of them (76%), and in none at MICs of 0.125, 0.25, and 1 μg/ml, respectively. Slightly better results were obtained for the ratio C(max)/MIC of ≥10. In conclusion, ciprofloxacin demonstrates excellent penetration into bronchial secretions. There is wide interindividual variability in its pharmacokinetic parameters in critically ill COPD patients and inadequate pharmacodynamic exposure against bacteria with MICs of ≥0.5 μg/ml.

Antibiotics in severely malnourished children: systematic review of efficacy, safety and pharmacokinetics

To systemically review the evidence in support of World Health Organization guidelines recommending broad-spectrum antibiotics for children with severe acute malnutrition (SAM). CENTRAL, MEDLINE, EMBASE, LILACS, POPLINE, CAB Abstracts and ongoing trials registers were searched. Experts were contacted. Conference proceedings and reference lists were manually searched. All study types, except single case reports, were included. Two randomized controlled trials (RCTs), one before-and-after study and two retrospective reports on clinical efficacy and safety were retrieved, together with 18 pharmacokinetic studies. Trial quality was generally poor and results could not be pooled due to heterogeneity. Oral amoxicillin for 5days was as effective as intramuscular ceftriaxone for 2days (1 RCT). For uncomplicated SAM, amoxicillin showed no benefit over placebo (1 retrospective study). The introduction of a standardized regimen using ampicillin and gentamicin significantly reduced mortality in hospitalized children (odds ratio, OR: 4.0; 95% confidence interval, CI: 1.7-9.8; 1before-and-after study). Oral chloramphenicol was as effective as trimethoprim-sulfamethoxazole in children with pneumonia (1 RCT). Pharmacokinetic data suggest that normal doses of penicillins, cotrimoxazole and gentamicin are safe in malnourished children, while the dose or frequency of chloramphenicol requires adjustment. Existing evidence is not strong enough to further clarify recommendations for antibiotic treatment in children with SAM. Large RCTs are needed to define optimal antibiotic treatment in children with SAM with and without complications. Further research into gentamicin and chloramphenicol toxicity and into the pharmacokinetics of ceftriaxone and ciprofloxacin is also required.

Ciprofloxacin Pharmacokinetics in Subjects with Normal and Impaired Renal Function

Ciprofloxacin Pharmacokinetics in Subjects with Normal and Impaired Renal Function

Pharmacokinetic interactions between ciprofloxacin and itraconazole in healthy male volunteers

To investigate the pharmacokinetic interaction between ciprofloxacin and itraconazole in healthy male volunteers. Ten healthy male volunteers were assigned into a 2-sequence, 3-period pharmacokinetic interaction study. In phase 1, all subjects were randomly assigned to receive 500 mg of ciprofloxacin alone and 200 mg of itraconazole alone twice daily for 7 days with a 14 day wash-out period in a crossover design. Phase 2 was performed 14 days after finishing phase 1, all subjects received 500 mg of ciprofloxacin in combination with 200 mg of itraconazole twice daily for 7 days. Ciprofloxacin and itraconazole pharmacokinetics were studied and adverse effects noted. Ciprofloxacin significantly increased the C(max) and AUC(0 - ∞) of itraconazole by 53.13% and 82.46%, respectively. The half-life and CL of itraconazole were not changed significantly. The combination of itraconazole and ciprofloxacin could therefore result in an increase in adverse drug reactions. Conversely, itraconazole had no significant effect on the pharmacokinetics of ciprofloxacin. Ciprofloxacin decreases the metabolism of itraconazole, most likely through inhibition of CYP3A4. The dosage of itraconazole should be reduced and its therapeutic outcome should be monitored closely when these two agents are concomitantly administered.

Ciprofloxacin Use in Neonates

ciprofloxacin has no marketing authorization for use in neonates worldwide but it is prescribed for the treatment of neonatal life-threatening infections, mainly in developing countries and in Europe. Given the concerns about its toxicity in this population and the necessity for its use in specific clinical situations, we conducted a systematic review of the use of ciprofloxacin in neonates. we performed a systematic search of PubMed, Embase, and the Cochrane Database of Systematic Reviews and bibliographies of relevant articles. We included all studies, regardless of design, that reported efficacy, safety, and pharmacokinetics of ciprofloxacin for the treatment of any neonatal infectious condition. We excluded letters, editorials, preliminary reports, and abstracts. observational cohort studies, case reports, and descriptions of patient series account for all literature reviewed. Ciprofloxacin was administrated in neonates as a salvage therapy for sepsis due to multidrug-resistant strains or with signs of clinical deterioration under first-line antibiotic treatment. Initial administration was always intravenous with variable dosing schedule. Clinical response to treatment was estimated at 64% and 91% in 2 cohort studies, with a median of 83% in case series. Of the 14 case reports, 12 yielded positive clinical outcomes. No serious adverse events, particularly joint toxicity, were observed, although evaluation was predominantly clinical and follow-up limited to few months after the end of treatment. the current literature provides some information to support the use of ciprofloxacin in neonates. Additional high quality studies should be undertaken to provide reliable data on pharmacokinetics, efficacy, and long-term safety.

Removal of residual colonic ciprofloxacin in the rat by activated charcoal entrapped within zinc-pectinate beads

Residual antibiotics reaching the colon have many deleterious effects on the colonic microbiota including the selection of new antibiotic resistances. In order to avoid the selection of ciprofloxacin resistance, intestine or colon-targeted zinc-pectinate beads containing activated charcoal (AC) were designed for the inactivation of residual ciprofloxacin in the gastrointestinal tract of rats. Bead stability after oral administration was adjusted by tuning the concentration of zinc in the gelling bath and the number of washings. Intestine and colon-targeted beads were administered along with 50 mg/kg of ciprofloxacin and ciprofloxacin was dosed in the plasma and the feces using HPLC. Ciprofloxacin pharmacokinetics was not affected by the oral co-administration of beads. The co-administration of intestine-targeted beads led to a significant decrease of the residual fecal free ciprofloxacin with a pronounced dose effect. Our study suggests the rat model is not appropriate for the investigation of bacteria responsive colon-targeted beads probably due to the important anatomical and physiological differences between human and rat gastrointestinal tracts. The ability of AC loaded zinc-pectinate beads to selectively decrease the intestinal residual fraction of ciprofloxacin could provide a better protection of the intestinal microbiota and may prevent the emergence of ciprofloxacin resistance in the gastrointestinal tract.

Pharmacokinetics and toxicity of ciprofloxacin in adult horses

Using a randomized, cross-over study design, ciprofloxacin was administered i.g. to eight adult mares at a dose of 20 mg/kg, and to seven of the eight horses at a dose of 5 mg/kg by bolus i.v. injection. The mean C(0) was 20.5 μg/mL (±8.8) immediately after i.v. administration. The C(max) was 0.6 μg/mL (±0.36) at T(max) 1.46 (±0.66) h after the administration of oral ciprofloxacin. The mean elimination half-life after i.v. administration was 5.8 (±1.6) h, and after oral administration the terminal half-life was 3.6 (±1.7) h. The overall mean systemic availability of the oral dose was 10.5 (±2.8)%. Transient adverse effects of mild to moderate severity included agitation, excitement and muscle fasciculation, followed by lethargy, cutaneous edema and loss of appetite developed in all seven horses after i.v. administration. All seven horses developed mild transient diarrhea at 36-48 after i.v. dosing. All eight horses dosed intragastrically experienced adverse events attributable to ciprofloxacin administration. Adverse events included mild transient diarrhea to severe colitis, endotoxemia and laminitis necessitating euthanasia of three horses on humane grounds. The high incidences of adverse events preclude oral and rapid i.v. push administration of ciprofloxacin.

Highly Sensitive Chemiluminescence Detection of Norfloxacin and Ciprofloxacin in CE and Its Applications

A highly sensitive and rapid method for the determination of norfloxacin and ciprofloxacin was developed using capillary electrophoresis coupled with chemiluminescence detection. The chemiluminescence detection was based on the enhancing effects of two analytes on the luminol-hydrogen peroxide reaction. The baseline separation of norfloxacin and ciprofloxacin was obtained within 4.5 min under the optimum conditions. The limits of detection (S/N = 3) of norfloxacin and ciprofloxacin were 2.9 × 10−10 and 1.1 × 10−12 mol L−1, respectively. The method showed wide linear range with four orders of magnitude (R ≥ 0.9982). The limits of quantification (S/N = 10) of two analytes in human urine samples were 6.0 × 10−8 and 5.1 × 10−10 mol L−1, respectively. The proposed method was successfully applied to the analysis of norfloxacin and ciprofloxacin in human urine samples and the monitoring of pharmacokinetics of ciprofloxacin in human body.

811 A COMPARATIVE PHARMACOKINETIC STUDY OF SEVEN BRANDS OF CIPROFLOXACIN IN NZW RABBITS USING LIQUID CHROMATOGRAPHY MASS SPECTROMETRY TECHNIQUE

You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Prostate & Genitalia1 Apr 2010811 A COMPARATIVE PHARMACOKINETIC STUDY OF SEVEN BRANDS OF CIPROFLOXACIN IN NZW RABBITS USING LIQUID CHROMATOGRAPHY MASS SPECTROMETRY TECHNIQUE Elijah Kehinde, Mohammed Abdel-Hamid, Oludotun Philips, Leyla Sharaf, and Alice Babu Elijah KehindeElijah Kehinde Safat, Kuwait More articles by this author , Mohammed Abdel-HamidMohammed Abdel-Hamid Kuwait, Kuwait More articles by this author , Oludotun PhilipsOludotun Philips Kuwait, Kuwait More articles by this author , Leyla SharafLeyla Sharaf Kuwait, Kuwait More articles by this author , and Alice BabuAlice Babu Kuwait, Kuwait More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1487AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The quinolones have been used widely in urological practice as prophylactic antibiotics prior to TRUS biopsy of the prostate and in the treatment of established susceptible uropathogens. Increasing resistance to the quinolones especially ciprofloxacin (CIP) is becoming a common problem in many urology units for possibly many reasons including the widespread use of generic substitutes. In this study we evaluated the pharmacokinetic behavior and the bioavailability of six generic brands of CIP in comparison to a reference branded product in NZW rabbits. METHODS A rapid and selective positive electrospray liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the determination of the total concentration of ciprofloxacin (unbound and protein-bound) in rabbit serum was applied. The developed method was conducted using XTerraR RP C8 column and a mobile phase of acetonitrile/water/formic acid in a ratio 80:20:0.025v/v/v at a flow rate 0.4 ml/min. Sample analysis was completed within 5 minutes. A preliminary protein precipitation procedure was applied to clean up the serum samples before analysis. Quantification was achieved by internal standard calibration using rufloxacin (RUF) as an internal standard (IS). Detection of CIP and IS was achieved using multiple reaction monitoring (MRM) at m/z 332.7>245.5 and m/z 364.7>263.2, respectively. Pharmacokinetics of CIP were evaluated in NZW rabbits following intra-gastric administration of 7 CIP brands. Generic CIP products used were obtained from the USA, Canada, UK, Egypt, Kuwait and Nigeria. RESULTS The developed method showed a good linearity (r >0.99), precision (RSD<6.1%) and accuracy (Bias <8.5%) over the concentration range of 0.5-6 μg/ml with a lower limit of quantification of 0.5 μg/ml and recovery between 93.5 and 108.5%. The specificity was proved by the absence of interference of endogenous serum constituents. Pharmacokinetic studies indicated that the % relative bioavailability of the generic brands was 33.1 to 77.5% compared to the branded reference product. CONCLUSIONS This study showed that there is a wide variation in the absorption patterns and possibly the therapeutic efficacy of the generic products of CIP compared to the branded reference product. Part of the explanation for increasing bacterial resistance to CIP may be due to the widespread use of generic CIP products with reduced efficacy and safety. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byKehinde E, Al-Maghrebi M, Sheikh M and Anim J (2018) Combined Ciprofloxacin and Amikacin Prophylaxis in the Prevention of Septicemia After Transrectal Ultrasound Guided Biopsy of the ProstateJournal of Urology, VOL. 189, NO. 3, (911-915), Online publication date: 1-Mar-2013. Volume 183Issue 4SApril 2010Page: e316-e317 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.Keywordsrabbit serumliquid chromatographymass spectrometryCiprofloxacinpharmacokineticMetricsAuthor Information Elijah Kehinde Safat, Kuwait More articles by this author Mohammed Abdel-Hamid Kuwait, Kuwait More articles by this author Oludotun Philips Kuwait, Kuwait More articles by this author Leyla Sharaf Kuwait, Kuwait More articles by this author Alice Babu Kuwait, Kuwait More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Comparative pharmacokinetics of enrofloxacin and ciprofloxacin in lactating dairy cows and beef steers following intravenous administration of enrofloxacin

The comparative pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin were investigated in lactating cows and beef steers. The plasma elimination half-life of either enrofloxacin or ciprofloxacin was shorter in cows than in steers. The overall production of ciprofloxacin was slightly higher in steers than in cows (metabolite ratio: 64% and 59%, respectively). There was no significant difference in plasma protein binding of enrofloxacin between cows (percent bound: 59.4%) and steers (percent bound: 60.8%). Ciprofloxacin was more extensively bound to plasma proteins in steers (percent bound: 49.6%) than in cows (percent bound: 33.8%). The steady state volume of distribution of enrofloxacin is comparable in cows (1.55 L/kg) and steers (1.59 L/kg). Within either bovine class, plasma elimination half-life of enrofloxacin and ciprofloxacin are comparable, while plasma protein binding was higher for enrofloxacin than for ciprofloxacin. Ciprofloxacin was more concentrated in milk than enrofloxacin.

Ciprofloxacin Pharmacokinetics in Critically Ill Patients

Survey of Anesthesiology: August 2009 - Volume 53 - Issue 4 - p 153 doi: 10.1097/SA.0b013e3181ab4c84

The Administration of Ciprofloxacin During Continuous Renal Replacement Therapy: Pilot Study

Continuous renal replacement therapy (CRRT) is a common technique in critically ill patients. However, there is no uniformity in the pharmacokinetics of ciprofloxacin (CPFX) used during CRRT. The aims of the present study were to estimate the pharmacokinetics of CPFX and to determine the appropriate administration of CPFX for critically ill patients undergoing CRRT. The pharmacokinetics of ciprofloxacin total clearance (CL(tot)) was calculated based on the creatinine clearance (CL(cre)), dialysate flow (QD), and ultrafiltrate flow (QF) as follows: CL(tot(L/h)) = (4.83 CL(cre(L/h)) + 6.41) + 0.92 (QD + Q(F(L/h))) based on in vitro study using CRRT circuit model. We administered CPFX to critically ill patients based on the CL(tot), which was 50 x CL(tot(L/h)) (mg/day). We confirmed that the CPFX concentrations reached higher than optimal concentrations, and infection was successfully controlled in these patients.

Effect of a Kampo Preparation, Byakkokaninjinto, on Pharmacokinetics of Ciprofloxacin and Tetracycline

The effect on the bioavailability of the antimicrobial agents (ciprofloxacin and tetracycline), which are well known to form chelates with cationic metals such as calcium, was evaluated in 20 healthy male volunteers according to an open, random crossover fashion using a Kampo preparation, byakkokaninjinto (TJ-34) which contains various cationic metals including calcium. Each subject received a single oral dose of tetracycline (250 mg) alone or ciprofloxacin (200 mg) alone along with a single coadministration of one pack (3 g) of the Kampo preparation, at one-week intervals. Concentrations of the drugs in plasma and urine were analyzed by HPLC. Concomitant administration of the Kampo preparation significantly decreased the peak plasma concentration (C(max)) and area under the plasma concentration-time curves (AUC), but not time to reach C(max) (T(max)), of ciprofloxacin and tetracycline. However, the decrease in bioavailability of ciprofloxacin was slight (15%) compared with that of tetracycline (30%). The Kampo preparation significantly decreased the urinary recovery of tetracycline, but not ciprofloxacin, and it had no effect on the renal clearance of either ciprofloxacin or tetracycline. These results indicate that the Kampo preparation tested in this study reduces the extent of bioavailability of ciprofloxacin and tetracycline, but not renal excretion, by decreasing the gastrointestinal absorption due to the formation of insoluble chelates with calcium. We recommend that the dose timing of the Kampo preparation should be carefully controlled to avoid therapeutic failure especially for patients receiving the treatment with tetracycline.

Ciprofloxacin pharmacokinetics in critically ill patients: A prospective cohort study

Purpose Optimal dosing of antibiotics is important for efficacy and avoidance of resistance. Fluoroquinolones are frequently used to treat severe infections in critically ill patients. We studied ciprofloxacin pharmacokinetics after administration of 400 mg twice a day (bid) intravenously (IV). Material and methods Serum concentrations were measured in 32 intensive care unit patients (age, 68.7 ± 17.4 years; Sepsis-related Organ Failure Assessment (SOFA) scores, 7.3 ± 3.4). Blood samples were drawn at 7 time points after ciprofloxacin infusion. We evaluated whether areas under the curve (AUCs) exceeded minimal inhibitory concentration (MIC) values of 0.125, 0.25, 0.5, 1.0, and 2.0 mg/L by 125 times and peak concentrations (C max) 10 × MIC (C max/MIC >10). Results The AUC/MIC more than 125 was achieved in 100% for MIC 0.125. For MIC values 0.25, 0.5, 1.0, and 2.0, results were 84%, 31%, 3%, and 0%, respectively ( P < .01). The C max/MIC more than 10 for MIC values of 0.125, 0.25, 0.5, 1.0, and 2.0 was realized in 100%, 97%, 69%, 25%, and 0%, respectively ( P < .01). Female sex, SOFA pulmonary points, and SOFA renal points predicted higher AUC. Cumulative SOFA scores were most predictive of high AUCs. Conclusions Ciprofloxacin 400 mg bid IV leads to inadequate AUC/MIC and C max/MIC ratios in many cases. Effective killing concentrations were only achieved in pathogens with MIC less than 0.25. As bacteria in intensive care unit patients often exceed this threshold, we recommend to use higher doses of ciprofloxacin (1200 mg daily) to ensure optimal bacterial killing and avoid antibiotic resistance.

Pharmacokinetics of topically applied ciprofloxacin in tears of mesocephalic and brachycephalic dogs

To evaluate the pharmacokinetics of ophthalmic ciprofloxacin in the tear film of normal mesocephalic and brachycephalic dogs. Twenty mesocephalic dogs and 15 brachycephalic dogs. Thirty-five microliters of ciprofloxacin were placed on the cornea of both eyes of each dog. Five brachycephalic dogs were used twice. A tear-test strip placed in the ventral cul de sac for 30 s was used to obtain samples. The tear film of each eye was sampled once at eight time-points post administration, resulting in five samples at each time-point. Samples were evaluated using high performance liquid chromatography. Data from the two skull types were compared using the unpaired two-tailed t-test. The mean concentration of ciprofloxacin in the tears of mesocephalic dogs was 192.8 +/- 269.97, 140.6 +/- 91.06, 56.60 +/- 28.47, 13.6 +/- 6.3, 43.25 +/- 59.71, 16.6 +/- 10.62, 15.6 +/- 13.16 and 6.25 +/- 9.84 microg/g at 5, 10, 15, 30 min and 1, 2, 4 and 6 h, respectively. The mean concentration of ciprofloxacin in the tears of brachycephalic dogs was 272.6 +/- 106.21, 144.4 +/- 142.32, 131.2 +/- 147.07, 75 +/- 80.07, 40.8 +/- 30.35, 35 +/- 21.98, 52.75 +/- 51.87 and 8.6 +/- 12.10 microg/g at 5, 10, 15, 30 min and 1, 2, 4 and 6 h, respectively. There was no statistical difference in tear concentration at any time-point between skull types. Topical application of ciprofloxacin resulted in a mean tear concentration of ciprofloxacin that remained above the MIC(90) levels for most pathogenic bacteria for 6 h in normal mesocephalic and brachycephalic dogs.