Plasma Concentrations Of Ciprofloxacin Research Articles

Comparative Pharmacokinetics of Intravenous Enrofloxacin in One- Six- And Twelve-Month-Old Sheep.

Enrofloxacin (ENR) is a fluoroquinolone antibiotic approved for use in sheep of all ages. The body composition and metabolic capability change with age. These changes may alter the pharmacokinetics of drugs and thus their effect. Therefore, the pharmacokinetics of drugs need to be established in target- age animals. To determine the pharmacokinetics of ENR and its active metabolite, ciprofloxacin (CIP), following a single intravenous administration of ENR at a dose of 10 mg/kg in different ages of sheep. The study was carried out in the one-, six- and twelve-month age period of the sheep. A single dose of 10 mg/kg ENR was administered intravenously through the jugular vein to sheep in all age periods. ENR and CIP plasma concentrations were determined using HPLC-UV and analyzed using a non-compartmental method. ENR was detected in the plasma until 36 h in one-month-old and up to 24 h in other ages. CIP was detected in the plasma up to 24 h in all age groups. The t1/2ʎz and Vdss were significantly higher in one-month-old sheep than in six and twelve-months old sheep. There was no difference in ClT and AUC values in different age groups. AUC0-∞CIP/AUC0-∞ENR ratios were higher in one-month-old than in six- and twelve-months sheep. The most important pharmacokinetic changes associated with aging in sheep are decreased Vdss and t1/2ʎz of ENR and the low ratio metabolizing of ENR to CIP. Pharmacokinetic/pharmacodynamic data showed that ENR after IV administration of 10 mg/kg dose provided the optimal AUC0-24/MIC90 ratios for E. coli, P. multocida and Mycoplasma spp. (>125) with MIC of 0.37 µg/mL and for S. aureus (>30) with MIC of 0.5 µg/mL in all ages of sheep.

Impact of mucositis on oral bioavailability and systemic exposure of ciprofloxacin Gram-negative infection prophylaxis in patients with haematological malignancies.

Patients with haematological malignancies frequently endure neutropenia and gastrointestinal (GI)-mucositis after high-dose chemotherapy. In these patients, ciprofloxacin is used for Gram-negative infection prophylaxis. We investigate ciprofloxacin pharmacokinetics after oral administration in patients with haematological malignancies and explore the impact of GI-mucositis on oral bioavailability and clearance in order to assure adequate systemic exposure. Adult haematological patients from two Dutch University Medical Centres received 500 mg twice daily oral ciprofloxacin for Gram-negative prophylaxis. The ciprofloxacin plasma concentrations were collected at various timepoints after oral ciprofloxacin administration and at various days after completion of chemotherapy. Data obtained after oral and intravenous ciprofloxacin administration in 28 healthy volunteers without mucositis served as a control group (391 samples). For haematological patients the degree of GI-mucositis was assessed using the Daily Gut Score (DGS), plasma citrulline and albumin. Data were analysed by non-linear mixed-effects modelling. In total, 250 blood samples were collected in 47 patients with a wide variety of haematological malignancies between 0-30 days after start of chemotherapy. Mucositis was generally mild [DGS median (IQR) 1 (1-1) and citrulline 16 μmol/L (12-23)]. The time to Cmax was slower in haematological patients compared with healthy volunteers although no association with the degree of mucositis (defined as DGS or citrulline) could be identified. Ciprofloxacin bioavailability and clearance were 60% and 33.2 L/h, respectively. This study supports oral dosing of ciprofloxacin as Gram-negative infection prophylaxis in haematological patients with mild-to-moderate mucositis capable of oral intake.

Development and Validation of a Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) Assay for the Determination of Total and Unbound Ciprofloxacin Concentrations in Human Plasma.

Although unbound ciprofloxacin is responsible for antibacterial effects, assays measuring the unbound drug plasma concentrations are scarce. This study aimed to develop and validate a rapid, reproducible, and sensitive liquid chromatography-tandem mass spectrometry assay for the determination of total and unbound ciprofloxacin plasma concentrations. The determination of total ciprofloxacin concentrations required a 10 μL sample, while for unbound ciprofloxacin concentrations, it was 100 μL. Unbound ciprofloxacin was separated from protein-bound ciprofloxacin through ultrafiltration. A deuterated internal standard was used, and the sample preparation involved protein precipitation. The method was fully validated over a concentration range of 0.02-5.0 mg/L, according to the US Food and Drug Administration guidelines. In addition, its clinical application was demonstrated. The total run time was 1.5 minutes. For total ciprofloxacin plasma concentrations, the mean accuracy ranged from 94.5% to 105.0% across the validated range, the intraday imprecision was ≤7.6%, and the interday imprecision was ≤9.8%. For unbound ciprofloxacin plasma concentrations, the mean accuracy ranged from 92.8% to 102.1% across the validated range, the intraday imprecision was ≤7.0%, and the interday imprecision was ≤9.6%. Ciprofloxacin in plasma and ultrafiltrate remained stable for at least 96 hours at room temperature, at least 4 years at -80°C, and at least 3 freeze/thaw cycles (-80°C), with a minimum interval of 24 hours. The presented method is precise and accurate. It has been implemented in clinical care and research projects at a university hospital, permitting rapid determination of total and unbound ciprofloxacin.

The effect of ketoprofen on the plasma concentration and pharmacokinetic parameters of ciprofloxacin in chickens

Ciprofloxacin (CFX) and ketoprofen (KPN) are used widely in combination in veterinary interventions for bacterial infections, so in this study the effect of KPN was studied on the efficacy of CFX, by measuring its plasma concentration and pharmacokinetic parameters in 7-10 day-old chickens. The analgesic median effective dose (ED50) of KPN was determined to be 1.62 mg/kg, IM, in the chickens. The preferable analgesic dose of KPN to be used with CFX was 4 mg/kg, IM, which differs significantly from KPN 2 mg/kg, IM,. The CFX plasma concentrations alone (8 mg/kg, IM) measured at different times (0.5, 1, 2, 4 and 24 hours) were 3.31, 3.60, 3.21, 2.70 and 0.17 μg/mL while its concentration was elevated by 53, 54, 90, 107 and 418 % when coadministered with KPN (4 mg/kg, IM) to 5.05, 5.53, 6.10, 5.59 and 0.88 μg/mL in the chickens, respectively. CFX pharmacokinetic parameters, such as the area under the curve (AUC), the area under the moment curve (AUMC), mean residence time (MRT), half-life (t1/2β), Tmax, and Cmax increased when KPN was coadministered with CFX by 129, 289, 70, 49, 100 and 69 %, whereas the elimination rate constant (Kel), the volume of distribution at steady state (Vss) and clearance (Cl) decreased by 36, 34 and 58 %, respectively. It was concluded that coadministration of KPN alters the plasma concentration and the pharmacokinetic parameters of CFX, suggesting that the CFX dose can be reduced when used with KPN to achieve the desired concentration of CFX in the plasma, as an antibacterial for treatment of infected animals.

Effect of diclofenac on the pharmacokinetics of ciprofloxacin in quail

This study investigated the Pharmacokinetics of ciprofloxacin alone or with diclofenac sodium in adult Japanese quails. The quails divided into two groups, the first group was dosed intraperitoneally with 50 mg/kg of ciprofloxacin, the second group was injected by 50 mg/kg of ciprofloxacin intraperitoneally then directly injected intraperitoneally by diclofenac sodium at a dosage of 5 mg/kg. Plasma concentrations of ciprofloxacin were determined by the spectrophotometer at wavelength 290 nm. Co-admiration of ciprofloxacin with diclofenac lead to appearing ciprofloxacin in plasma at 12.02, 6.4, 5.3, 3.30, 1.36, 0.60 μg/ml in the periods of 0.25, 0.50, 1, 2, 4 and 8 hours post-injection. A significantly increased in the concentration of ciprofloxacin at times of 0.25, 0.50, 1, and 2 hours post-injection and appeared at a concentration of 6.96, 3.09, 2.2, and 0.72 μg/ml. The pharmacokinetics of ciprofloxacin when given with diclofenac sodium was represented by 91% decrease in elimination constant rate, 53% decrease in elimination half-life t1/2, 64% decrease in volume of distribution to steady-state, 22% decrease in clearance, 28% increase area under curve, 41% decrease in area under moment curve, 53% decrease in mean residence time and 37% increase in maximum plasma concentration. Our study concludes that co-administration of ciprofloxacin with diclofenac sodium lead to alteration in some pharmacokinetic data of ciprofloxacin like effect on the plasma concentration and volume of distribution and clearance. This effect must be considered when therapy by ciprofloxacin with diclofenac, the co-administration of diclofenac with ciprofloxacin decrease the elimination of ciprofloxacin

Pharmacokinetic profile of enrofloxacin and its metabolite ciprofloxacin in Asian house geckos (Hemidactylus frenatus) after single-dose oral administration of enrofloxacin

The pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were determined following oral administration in 21 Asian house geckos (Hemidactylus frenatus) at a dose of 10 mg/kg. Changes in enrofloxacin and ciprofloxacin plasma concentrations were quantified at regular intervals over 72 h (1, 2, 6, 12, 24, 48, and 72 h). Samples were analysed by high-pressure liquid chromatography (HPLC) and the enrofloxacin pharmacokinetic data underwent a two-compartment analysis. Due to the limited ciprofloxacin plasma concentrations above the lower limit of quantification (LLOQ), the ciprofloxacin data underwent non-compartment analysis and the half-life was determined by the Lineweaver-Burke plot and analysis. The enrofloxacin and ciprofloxacin mean half-lives (t½) were 0.95 h (α) / 24.36 h (β), and 11.06 h respectively, area under the curve (AUC0-24h) were 60.56 and 3.14 µg/mL*h, respectively, maximum concentrations (Cmax) were 12.31 and 0.24 µg/mL, respectively, and time required to reach the Cmax (Tmax) were 1 and 2 h respectively. Enrofloxacin was minimally converted to the active metabolite ciprofloxacin, with ciprofloxacin concentrations contributing only 4.91% of the total fluoroquinolone concentrations (AUC0-24h). Based on the pharmacokinetic indices when using susceptibility breakpoints when determined at mammalian body temperature it is predicted that single oral administration of enrofloxacin (10 mg/kg) would result in plasma concentrations effective against susceptible bacterial species inhibited by an enrofloxacin MIC ≤ 0.5 µg/mL in vitro, but additional studies will be required to determine its efficacy in vivo.

Bioequivalence of Two Oral Formulations of Ciprofloxacin 250 mg Tablets in Healthy Mexican Volunteers

Background. There are numerous reports of low-quality formulations of ciprofloxacin in the market, which has been associated with therapeutic failure and the development of microbial resistance. Objective. The aim of this study is evaluating the bioequivalence between two oral immediate-release ciprofloxacin 250 mg tablets. Material and Methods. The study was performed in 24 Mexican healthy volunteers following a randomized cross over 2 × 2 design. Single doses of a test formulation Lemyflox® (Lemery Laboratories, Mexico) and the reference formulation Ciproxina® (Bayer, Mexico) were administered; blood samples were obtained during a 12 h period. Ciprofloxacin plasma concentrations were quantified using a validated High-Pressure Liquid Chromatography (HPLC) method, plasma concentration against time curves were constructed and pharmacokinetic parameters were determined by non-compartmental analysis. In order to determine bioequivalence, test/reference ratios of Cmax, AUC0-t and AUC0-inf were compared using analysis of variance (ANOVA), followed by the 90 % confidence intervals and the Schuirmann bilateral test. Results. The 90 % confidence intervals limits ranged from 82.92 to 100.88 % for Cmax, from 93.05 to 109.15 % for AUC0-t and from 97.76 to 114.99 % for AUC0-inf, all cases were within bioequivalence acceptance range of 80 - 125 %. Schuirmann test confirmed such observation as the probability that Cmax, AUC0-t and AUC0-inf ratios were beyond 80 - 125 % was lower than 0.05. Conclusions. The results obtained demonstrate bioequivalence between the test and reference formulations.

Penetration of Ciprofloxacin and Amikacin into the Alveolar Epithelial Lining Fluid of Rats with Pulmonary Fibrosis.

We determined the concentration-time profiles of ciprofloxacin and amikacin in serum and alveolar epithelial lining fluid (ELF) of rats with or without pulmonary fibrosis and investigated the effect of pulmonary fibrosis on the capacity for penetration of antimicrobials into the ELF of rats. Pulmonary fibrosis was induced in rats with a single intratracheal instillation of bleomycin. After intravenous injection of ciprofloxacin or amikacin, blood and bronchoalveolar lavage fluid samples were collected. Urea concentrations in serum and lavage fluid were determined using an enzymatic assay. Ciprofloxacin and amikacin concentrations were determined by high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry, respectively. The mean ratio of ELF to plasma concentrations of ciprofloxacin at each time point in the normal group did not significantly differ from that in the pulmonary fibrosis group. However, the ratio of the ciprofloxacin area under the concentration-time curve from 0 to 24 h (AUC0-24) in ELF to the AUC0-24 in plasma was 1.02 in the normal group and 0.76 in the pulmonary fibrosis group. The mean ELF-to-plasma concentration ratios of amikacin at each time point in the normal group were higher than those in the pulmonary fibrosis group, reaching a statistically significant difference at 1, 2, and 4 h. The ratio of the AUC0-24 in ELF to the AUC0-24 in plasma was 0.49 in the normal group and 0.27 in the pulmonary fibrosis group. In conclusion, pulmonary fibrosis can influence the penetration of antimicrobials into the ELF of rats and may have a marked effect on the penetration of amikacin than that of ciprofloxacin.

Development and Validation of an LC-MS/MS-ESI Method for Comparative Pharmacokinetic Study of Ciprofloxacin in Healthy Male Subjects.

A sensitive, specific and reproducible liquid chromatography coupled to tandem mass spectrometric method was developed and validated for the estimation of ciprofloxacin, an extensively used second-generation quinolone antibiotics, in human plasma. A liquid-liquid extraction of ciprofloxacin and the internal standard, ofloxacin, has been approached from the biological matrix using chloroform. Chromatographic separation was achieved in positive ion modes, isocratically on a 3.5 μm C18 analytical column (75 mm×4.6 mm, i.d.) with 0.2% formic acid solution in water: methanol (10:90, v/v) as mobile phase, at a flow rate of 0.5 mL.min-1. The MS/MS ion transitions were monitored as 332.0→231.3 for ciprofloxacin and 362.2→261.0 for IS. The method showed good linearity in the range of 0.01-5.00 μg.mL-1 (r2 >0.99) with a good precision (3.37-12.60%) and accuracy (87.25-114%). At the same time, ciprofloxacin was found to be stable during stability studies viz. bench-top, auto-sampler, freeze-thaw cycle and long-term. The developed and validated method was successfully applied to measure plasma ciprofloxacin concentrations in a single dose bioequivalence study.

Inhibitory Effects of Multiple-Dose Treatment with Baicalein on the Pharmacokinetics of Ciprofloxacin in Rats.

Ciprofloxacin is used as a treatment for urinary and respiratory tract infections in clinical practice. Baicalein, a major flavonoid present in Scutellaria baicalensis, is a well-known and potent antibacterial compound used in complementary and alternative medicine practices. The present study aimed to clarify the effects of multiple-dose treatment with baicalein on the pharmacokinetics of ciprofloxacin in rats. Following the oral administration of baicalein (20, 40, or 80 mg/kg) for five consecutive days, the rats received an oral administration of ciprofloxacin (20 mg/kg). Blood samples were collected at specific time points, and the plasma concentrations of ciprofloxacin were determined by using high-performance liquid chromatography. To evaluate the mechanisms underlying the interaction between baicalein and ciprofloxacin, a rhodamine 123 accumulation assay was performed in LS-180 cells. A pharmacokinetic study revealed that multiple-dose treatment with baicalein significantly decreased the peak serum concentration (Cmax ), area under the curve (AUC0 → 480 min ), and relative bioavailability (Frel ) of ciprofloxacin (p < 0.05). The rhodamine 123 accumulation assay revealed that treatment with baicalein for 48 h markedly reduced the intracellular accumulation of rhodamine 123. Taken together, these findings suggest that baicalein may result in the therapeutic failure of ciprofloxacin or other quinolone-based antibiotics used for chemotherapy in clinical practice. Copyright © 2016 John Wiley & Sons, Ltd.

Use of Modeling and Simulation Tools for Understanding the Impact of Formulation on the Absorption of a Low Solubility Compound: Ciprofloxacin.

This study explored the utility of mechanistic absorption models to describe the in vivo performance of a low solubility/low permeability compound in normal healthy subjects. Sixteen healthy human volunteers received three oral formulations and an intravenous infusion in a randomized crossover design. Plasma ciprofloxacin concentrations were estimated by HPLC. In vitro ciprofloxacin release from the oral tablets was tested under a variety of conditions. A mechanistic model was used to explore in vivo dissolution and intestinal absorption. Although dissolution rate influenced the location of drug release, absorption challenges appeared to be associated with permeability limitations in the lower small intestine and colon. The apparent relationship between drug solubilization within the upper small intestinal and formulation overall bioavailability suggested the presence of an intestinal absorption window in many individuals. Failure to absorb drug within this window appeared to be linked with the likelihood of in vivo drug precipitation. Challenges encountered during this modeling exercise included large intersubject variability in product in vivo dissolution and the apparent limitations in ciprofloxacin absorption. Although transporter activity was not included as a model parameter, this evaluation demonstrated how identifying the location of drug absorption across several formulations provided an opportunity to identify factors to consider when formulating similar low solubility/low permeability compounds. The use of mechanistic models was invaluable for our understanding of in vivo product performance and for the assessment of individual profiles rather than means. The latter was essential for understanding the potential challenges that may be encountered when introducing a formulation into a patient population.

Influence of Menstrual Cycle on Pharmacokinetics of Ciprofloxacin

The aim of our research work is to study the influence of menstrual cycle on the pharmacokinetic parameters of the Ciprofloxacin in patients with infections . Plasma samples were collected from 12 female patients on long term oral Ciprofloxacin monotherapy (not less than two years) with prescribed dosage regimen dose at the time points of 0, 1, 2, 3, 4, 6, 8 &12 hours after dosing and analysed for drug content by HPLC method. Mean Cmax of Ciprofloxacin was decreased by 20% in the ovulatory phase compared to that of follicular phase. The AUC0-∞ of Ciprofloxacin i.e, bioavailability was decreased in luteal phase by 20% than follicular phase. Volume of distribution of Ciprofloxacin was significantly lower in follicular and luteal phases compared to ovulatory phase. Ciprofloxacin half-life was decreased and clearance was increased in luteal phase compared to follicular phase. Except Vd/f and Vss/f, menstrual cycle phases did not significantly affect the pharmacokinetic profile of Ciprofloxacin in terms of Cmax, Tmax, AUC0-∞, AUMC0-∞, t1/2, MRT, clearance and absorption rate constant. From the above observations it can be concluded that, menstrual hormonal changes influenced Ciprofloxacin pharmacokinetics to a lesser extent and Vd/f and Vss/f were significantly altered. Mean plasma concentrations of Ciprofloxacin were higher in follicular phase than in ovulatory and luteal phases.

Factors Affecting Penetration of Ciprofloxacin in Lower Extremity Ischemic Tissues.

The aims of this study were to evaluate factors influencing the distribution of ciprofloxacin in tissue of patients suffering from varying degrees of peripheral arterial disease (PAD). Blood and tissue samples were collected from patients undergoing debridement or amputation procedures and the amount of ciprofloxacin in them was determined using high-performance liquid chromatography. All patients were administered a 200-mg dose of intravenous ciprofloxacin prior to the debridement or amputation procedure. Data, including patient gender, age, type of diabetes, presence of neuropathy, medications taken, and severity of PAD were collected. These data were then analyzed to determine factors influencing the concentrations of ciprofloxacin in tissue of the lower limbs. The Kruskal-Wallis test, Spearman correlation, and chi-square test were used to relate covariates and fixed factors with the concentration of ciprofloxacin in tissue. Following bivariate analysis, a 3-predictor regression model was fitted to predict tissue concentrations of ciprofloxacin given information about these predictors. Blood and tissue samples were collected from 50 patients having an average age of 68 years. Thirty-three patients were males and 35 patients suffered from type 2 diabetes. The average number of medications that these patients were taking was 10. The majority of patients (n = 35) were suffering from severe PAD. Tissue concentrations of ciprofloxacin were mainly related to plasma concentrations of ciprofloxacin, number of medications that the patients were taking and severity of PAD.

PHARMACOKINETICS OF SINGLE-DOSE ORALLY ADMINISTERED CIPROFLOXACIN IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

Ciprofloxacin is commonly selected for clinical use due to its broad-spectrum efficacy and is a frequently administered antibiotic at The Marine Mammal Center, a marine mammal rehabilitation facility. Ciprofloxacin is used for treatment of California sea lions ( Zalophus californianus ) suffering from a variety of bacterial infections at doses extrapolated from other mammalian species. However, as oral absorption is variable both within and across species, a more accurate determination of appropriate dosage is needed to ensure effective treatment and avoid emergence of drug-resistant bacterial strains. A pharmacokinetic study was performed to assess plasma concentrations of ciprofloxacin in California sea lions after a single oral dose. Twenty healthy California sea lions received a single 10-mg/kg oral dose of ciprofloxacin administered in a herring fish. Blood was then collected at two of the following times from each individual: 0.5, 0.75, 1, 2, 4, 8, 10, 12, 18, and 24 hr postingestion. Plasma ciprofloxacin concentration was assessed via high-performance liquid chromatography. A population pharmacokinetics model demonstrated that an oral ciprofloxacin dose of 10 mg/kg achieved an area under the concentration vs. time curve of 6.01 μg hr/ml. Absorption was rapid, with ciprofloxacin detectable in plasma 0.54 hr after drug administration; absorption half-life was 0.09 hr. A maximum plasma concentration of 1.21 μg/ml was observed at 1.01 hr, with an elimination half-life of 3.09 hr. Ciprofloxacin administered orally at 10 mg/kg produced therapeutic antibacterial exposure for only some of the most susceptible bacterial organisms commonly isolated from California sea lions.

Pharmacokinetic Parameters of Ciprofloxacin in Bangladeshi Volunteers: A Preliminary Evaluation

The present study has attempted to establish a High-performance liquid chromatography (HPLC) method to determine ciprofloxacin in plasma, in order to evaluate the bioavailability of ciprofloxacin. In this study, initially 8 (eight) Bangladeshi Bangalee healthy male volunteers and 7 (seven) Bangladeshi Tribal healthy male volunteers received 500 mg tablet of pioneer brand of ciprofloxacin in oral route. Blood samples were collected at 0, 30, 60, 120, 180, 360, 540 and 720 minutes after drug administration. After 1 week of washout period, same volunteers of two groups received 200 mg injection of pioneer brand of ciprofloxacin in intravenous route. HPLC with ultraviolet detection was used to quantify plasma ciprofloxacin concentrations. In case of oral route, AUC0–12h, Cmax, Tmax and T1/2 values for Bangladeshi Bangalee and Tribal healthy volunteers were 545.53 ± 32.35 &amp; 655.74 ± 16.57 ?g min/mL, 2.19 ± 0.16 &amp; 2.49 ± 0.20 ?g/mL, 75.00 ± 27.77 &amp; 94.29 ± 32.07 min and 241.96 ± 13.53 &amp; 242.02 ± 19.88 min respectively. In case of intravenous route, the AUC0–12h, Cmax, Tmax and T1/2 values for Bangladeshi Bangalee and Tribal healthy volunteers were 344.07 ± 29.31 &amp; 343.31 ± 25.34 ?g min/mL, 2.47 ± 0.17 &amp; 2.46 ± 0.18 ?g/mL, 30.00 ± 0.00 &amp; 30.0 ± 0.0 min and 278.16 ± 1.74 &amp; 272.74 ± 4.42 min respectively and the difference between these two groups of volunteers was not significant. The difference in AUC0–12h, Cmax, Tmax and T1/2 values between these two groups of volunteers was significant. The mean percent absolute bioavailability in Bangladeshi Bangalee and Tribal healthy volunteers was 64.04 ± 3.21 and 76.81 ± 6.71 respectively. In conclusion, pharmacokinetic parameters of ciprofloxacin significantly varied among Bangladeshi Bangalee and Bangladeshi Tribal healthy volunteers indicating necessity of further study on population pharmacokinetic in these groups of people. DOI: http://dx.doi.org/10.3329/bjpp.v27i1-2.20066 Bangladesh J Physiol Pharmacol 2011;27(1&amp;2):1-8.

Pharmacokinetics and pharmacodynamics of ciprofloxacin in critically ill patients after the first intravenous administration of 400 mg

To investigate the pharmacokinetics and pharmacodynamics of ciprofloxacin in critically ill patients after the first intravenous administration of 400 mg. Plasma concentrations were measured in 20 critically ill patients (mean [SD]; age, 55.5 [16.5] years; weight, 80.3 [16.9] kg; and creatinine clearance, 110.0 [71.5] mL/min). Four blood samples were drawn at the following time points 0, 0.5, 6 , 8 hours after infusion. Ciprofloxacin concentrations were determined by high-performance liquid chromatography. In the cases where ciprofloxacin was applied in targeted antibiotic therapy the minimum inhibitory concentrations (MIC) were ≤0.5 mg/l. The maximum and minimum plasma concentrations of ciprofloxacin were 1.74 (0.58-7.90) and 0.45 (0.16-2.96) mg/l, respectively. The main pharmacokinetic parameters for ciprofloxacin in the analyzed patients were as follows: k(el), 0.21 h-1; t(1/2kel), 3.37 h; AUC(0-inf), 10.10 mg×h/l; AUMC(0-last), 15.36 mg×h(2)/l; MRT, 1.71 h; V(d), 214.8 l; Cl, 39.70 l/h. Considering the maximum value of MIC (0.5 mg/l) only 30% and 25% of analyzed patients had desired values of the PK/PD indexes AUIC>125 and C(max) /MIC>10, respectively. The target plasma concentrations after the first dose of ciprofloxacin were reached only in a few critically ill patients. Considerable inter-subject variability for PK/PD parameters in ICU patients requires systematic monitoring.

Pharmacokinetics and Bioequivalence Evaluation of Two Brands of Ciprofloxacin 500 mg Tablets in Iranian Healthy Volunteers

In the present study pharmacokinetics and bioequivalence of 2 brands of ciprofloxacin 500 mg were evaluated in 24 healthy male volunteers after a single dose oral administration in an open, randomized, 2-way crossover study.Blood samples were taken before and within 12 h after the administration of the drug. Plasma concentrations of ciprofloxacin were determined by a simple HPLC method with ultraviolet detection. The used method was validated for specificity, accuracy, precision and sensitivity. The mobile phase consisted of 0.025 M phosphoric acid, acetonitrile, and triethylamine. Analytical column was 5 μm Eurosphere C8 with a Eurosphere C8 guard column. The detector wavelength was set at 278 nm and the retention time was 10 min. The pharmacokinetic parameters, including peak plasma concentrations and time needed to reach the peak were obtained directly from plasma concentration-time profiles. The area under the curve was calculated using non-compartmental methods.The Cmax of 1476.8±319.9 ng/mL and 1 423.0±278.4 ng/mL were attained in about 1.67 and 1.58 h for test and reference formulations, respectively. The mean±SD values for AUC0-∞ were 9 665.3±2 880.2 and 9 716.1±2 572.1 ng.hr/mL for test and reference formulations, respectively. The pharmacokinetics parameters AUC0-t, AUC0-∞ and Cmax were calculated for bioequivalence after log-transformation of data. The 90% confidence intervals of test/reference for AUC0-t, AUC0-∞ and Cmax were (95.6-109.9%), (91.8-106.3%) and (95.2-112.8%), respectively and all were within the bioequivalence acceptance range of 80-125%.These results indicate that 2 tested formulations are bioequivalent and thus could be prescribed interchangeably.

Effect of total and partial nephrectomy on the elimination of ciprofloxacin in humans

BackgroundRenal cell carcinoma (RCC) is the most common form of kidney cancer. Surgery is a standard procedure to resect the tumor during total (TN) or partial (nephron-sparing) nephrectomy (PN). Ciprofloxacin is most often administered at the usual intravenous dose of 100–400mg/12h. The application of such low doses of ciprofloxacin as 200mg/24h carries the risk of achieving subtherapeutic concentrations even in patients with limited renal function. The aim of the study was a comparison of concentrations and pharmacokinetics for ciprofloxacin at steady-state in patients after total and partial nephrectomy and evaluation of the effectiveness of the iv dose 200mg/24h against the theoretical value of MIC, 0.5μg/ml. MethodsThe research was carried out on two groups of patients after nephrectomy: total (group 1, n=21; mean [SD], age, 62.9 [14.4] years; weight, 76.0 [14.6]kg; creatinine clearance, clcr, 90.7 [22.2]ml/min) and partial (group 2, n=15; 61.7 [9.3] years; 87.8 [16.4]kg; CLCR, 107.8 [36.4]ml/min). The patients were treated with ciprofloxacin in the dose of 200mg/24h (iv). Plasma concentrations of ciprofloxacin at steady state were measured with validated HPLC method with UV detection. ResultsThe mean values of plasma concentrations of ciprofloxacin at steady state in group 1 and 2 were: Cssmax, 2.012 and 1.345; Cssmin, 0.437 and 0.244μg/ml, respectively. The main pharmacokinetic parameters for ciprofloxacin in group 1 and 2 were as follows: AUC(0–last), 30.9 [17.9] and 19.5 [8.7]μgh/ml; AUMC(0–last), 177.91 [11.1] and 91.9 [66.5]μgh2/ml; t1/2β, 13.9 [7.7] and 9.8 [3.3]h; MRT, 16.5 [12.1] and 9.77 [5.4]h; Vd, 115.0 [67.2] and 142.2 [78.7]l; CL, 6.2 [3.3] and 10.8 [5.7]l/h, respectively. With the assumed MIC=0.5μg/ml, the values of Cssmax/MIC<10 and AUC/MIC<125 were obtained in all the patients. ConclusionIn our patients we observed significant differences in some pharmacokinetic parameters of ciprofloxacin after two types of nephrectomy.

Dosing regimens of oral ciprofloxacin for children with severe malnutrition: a population pharmacokinetic study with Monte Carlo simulation

BackgroundSevere malnutrition is frequently complicated by sepsis, leading to high case fatality. Oral ciprofloxacin is a potential alternative to the standard parenteral ampicillin/gentamicin combination, but its pharmacokinetics in malnourished children is unknown.MethodsCiprofloxacin (10 mg/kg, 12 hourly) was administered either 2 h before or up to 2 h after feeds to Kenyan children hospitalized with severe malnutrition. Four plasma ciprofloxacin concentrations were measured over 24 h. Population analysis with NONMEM investigated factors affecting the oral clearance (CL) and the oral volume of distribution (V). Monte Carlo simulations investigated dosage regimens to achieve a target AUC0–24/MIC ratio of ≥125.ResultsData comprised 202 ciprofloxacin concentration measurements from 52 children aged 8–102 months. Absorption was generally rapid but variable; Cmax ranged from 0.6 to 4.5 mg/L. Data were fitted by a one-compartment model with first-order absorption and lag. The parameters were CL (L/h) = 42.7 (L/h/70 kg) × [weight (kg)/70]0.75 × [1 + 0.0368 (Na+ – 136)] × [1 – 0.283 (high risk)] and V (L) = 372 × (L/70 kg) × [1 + 0.0291 (Na+ – 136)]. Estimates of AUC0–24 ranged from 8 to 61 mg·h/L. The breakpoint for Gram-negative organisms was <0.06 mg/L with doses of 20 mg/kg/day and <0.125 mg/L with doses of 30 or 45 mg/kg/day. The cumulative fraction of response with 30 mg/kg/day was ≥80% for Escherichia coli, Klebsiella pneumoniae and Salmonella species, but <60% for Pseudomonas aeruginosa.ConclusionsAn oral ciprofloxacin dose of 10 mg/kg three times daily (30 mg/kg/day) may be a suitable alternative antibiotic for the management of sepsis in severely malnourished children. Absorption was unaffected by the simultaneous administration of feeds.

Determination of ciprofloxacin in human plasma using high-performance liquid chromatography coupled with fluorescence detection: Application to a population pharmacokinetics study in children with severe malnutrition

Clinical pharmacokinetic studies of ciprofloxacin require accurate and precise measurement of plasma drug concentrations. We describe a rapid, selective and sensitive HPLC method coupled with fluorescence detection for determination of ciprofloxacin in human plasma. Internal standard (IS; sarafloxacin) was added to plasma aliquots (200μL) prior to protein precipitation with acetonitrile. Ciprofloxacin and IS were eluted on a Synergi Max-RP analytical column (150mm×4.6mm i.d., 5μm particle size) maintained at 40°C. The mobile phase comprised a mixture of aqueous orthophosphoric acid (0.025M)/methanol/acetonitrile (75/13/12%, v/v/v); the pH was adjusted to 3.0 with triethylamine. A fluorescence detector (excitation/emission wavelength of 278/450nm) was used. Retention times for ciprofloxacin and IS were approximately 3.6 and 7.0min, respectively. Calibration curves of ciprofloxacin were linear over the concentration range of 0.02–4μg/mL, with correlation coefficients (r2)≥0.998. Intra- and inter-assay relative standard deviations (SD) were <8.0% and accuracy values ranged from 93% to 105% for quality control samples (0.2, 1.8 and 3.6μg/mL). The mean (SD) extraction recoveries for ciprofloxacin from spiked plasma at 0.08, 1.8 and 3.6μg/mL were 72.8±12.5% (n=5), 83.5±5.2% and 77.7±2.0%, respectively (n=8 in both cases). The recovery for IS was 94.5±7.9% (n=15). The limits of detection and quantification were 10ng/mL and 20ng/mL, respectively. Ciprofloxacin was stable in plasma for at least one month when stored at −15°C to −25°C and −70°C to −90°C. This method was successfully applied to measure plasma ciprofloxacin concentrations in a population pharmacokinetics study of ciprofloxacin in malnourished children.