Influence of Renal Failure on Intestinal Clearance of Ciprofloxacin in Rats

Dautrey, Sophie; Rabbaa, Lydia; Laouari, Denise; Lacour, Bernard; Carbon, C; Farinotti, Robert

doi:10.1128/aac.43.3.678

Cited by 9 publications

(3 citation statements)

References 14 publications

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“…Forrest et al [20] found a significant relationship between total ciprofloxacin clearance and CL Cr estimated by the Jelliffe formula, mostly in patients with lower respiratory tract infection. Additionally, when ciprofloxacin renal clearance is compromised, the transintestinal elimination route is frequently described in the literature in humans and animals as the main compensatory elimination route [38][39][40]. In septic patients, Jones et al [39] showed that only those patients who had liver or bowel pathology in addition to renal failure had a significantly higher serum concentration than all other patients.…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics and target attainment of ciprofloxacin in critically ill patients

Abdulla

Rogouti

Hunfeld

et al. 2020

Eur J Clin Pharmacol

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Purpose To develop and validate a population pharmacokinetic model of ciprofloxacin intravenously in critically ill patients, and determine target attainment to provide guidance for more effective regimens. Methods Non-linear mixed-effects modelling was used for the model development and covariate analysis. Target attainment of an ƒAUC 0-24 /MIC ≥ 100 for different MICs was calculated for standard dosing regimens. Monte Carlo simulations were performed to define the probability of target attainment (PTA) of several dosing regimens. Results A total of 204 blood samples were collected from 42 ICU patients treated with ciprofloxacin 400-1200 mg/day, with median values for age of 66 years, APACHE II score of 22, BMI of 26 kg/m 2 , and eGFR of 58.5 mL/min/1.73 m 2. The median ƒAUC 0-24 and ƒC max were 29.9 mg•h/L and 3.1 mg/L, respectively. Ciprofloxacin pharmacokinetics were best described by a two-compartment model. We did not find any significant covariate to add to the structural model. The proportion of patients achieving the target ƒAUC 0-24 /MIC ≥ 100 were 61.9% and 16.7% with MICs of 0.25 and 0.5 mg/L, respectively. Results of the PTA simulations suggest that a dose of ≥ 1200 mg/day is needed to achieve sufficient ƒAUC 0-24 /MIC ratios. Conclusions The model described the pharmacokinetics of ciprofloxacin in ICU patients adequately. No significant covariates were found and high inter-individual variability of ciprofloxacin pharmacokinetics in ICU patients was observed. The poor target attainment supports the use of higher doses such as 1200 mg/day in critically ill patients, while the variability of inter-individual pharmacokinetics parameters emphasizes the need for therapeutic drug monitoring to ensure optimal exposure.

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Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics and target attainment of ciprofloxacin in critically ill patients

Abdulla

Rogouti

Hunfeld

et al. 2020

Eur J Clin Pharmacol

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“…Enteral and hepatic elimination are obviously enhanced when renal clearance is reduced (7, 24). Dose reduction for patients with renal insufficiency and coexistent bowel/liver diseases has been recommended (16).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Ciprofloxacin in Patients with Acute Renal Failure Undergoing Continuous Venovenous Haemofiltration: Influence of Concomitant Liver Cirrhosis

et al. 2002

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To determine an adequate dosage of ciprofloxacin in critically ill medical patients on continuous venovenous haemofiltration, we studied the pharmacokinetics of ciprofloxacin in eight critically ill medical patients with renal failure treated with continuous venovenous haemofiltration using polysulfone membranes. Three of those patients also presented with severe liver dysfunction. For comparison, three patients with approximately normal renal function and two patients with impaired renal function were included. During haemofiltration, plasma concentrations of ciprofloxacin were variable. In all critically ill patients ciprofloxacin elimination was significantly slowed; the mean half-life was similarly prolonged to about 14 h in patients on haemofiltration and those with approximately normal renal function. In critically ill patients with impaired renal function not on haemofiltration, the mean half-life was longest. Ciprofloxacin clearance by haemofiltration was a quarter of the total clearance. Although a unique dose recommendation can hardly be made because of the high variability of pharmacokinetics during haemofiltration, a daily dose of 800 mg (400 mg b.i.d.) in average can be regarded as appropriated for reaching a target plasma concentration of 2 to 3 micrograms/mL (mean concentration). Because the half-life of ciprofloxacin was further prolonged by the presence of liver cirrhosis, the dose should be reduced to 600 mg in patients on haemofiltration with concomitant severe liver dysfunction.

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“…They are localized at the apical membrane of cells like P‐gp ( Tsui & Tamai, 1996 ) or at the basolateral membrane like OCT‐1 ( Zhang et al ., 1998 ). For this reason, in order to study the mechanism(s) involved in its intestinal elimination, ciprofloxacin was administered parenterally at a dose of 12.5 mg kg −1 (a dose which is compatible with a linearity of biliary and intestinal kinetics [ Dautrey et al ., 1999 ]) alone, and in the presence of different compounds potentially capable of interacting with it. These compounds were administered parenterally 15 min before ciprofloxacin in order to optimize diffusion into the different organs.…”

Section: Discussionmentioning

confidence: 99%

Active intestinal elimination of ciprofloxacin in rats: modulation by different substrates

Dautrey

Felice

Petiet

et al. 1999

British J Pharmacology

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1 Two in vivo models, in the rat, were used to investigate, in the presence of di erent substrates, the overall and net intestinal elimination of cipro¯oxacin: an open-intestinal perfusion model and an intestinal loop model respectively. 2 In the presence of quinidine, verapamil and cyclosporin (substrates of the P-glycoprotein (P-gp)), plasma AUCs of cipro¯oxacin were 1.5 ± 2 fold increased, while biliary clearance (1.5 ± 2 fold), intestinal overall and net clearances (2 ± 4 fold and 1.5 ± 8 fold respectively) decreased. The weak e ect obtained with cyclosporin as compared to verapamil and especially quinidine, suggests, for cipro¯oxacin, the existence of transport systems distinct from the P-gp, as the OCT1 transporter which could be inhibited by quinidine. 3 With cephalexin and azlocillin, two b-lactam antibiotics, plasma AUCs of cipro¯oxacin increased and biliary and intestinal overall clearances decreased in a similar fashion (1.3 ± 2 fold), suggesting the involvement of organic anion and/or cation transporters. 4 In the presence of structural analogues, the e ect was dependent on the compound administered: Spar¯oxacin had no e ect on intestinal clearance of cipro¯oxacin. In contrast, with pe¯oxacin, overall intestinal clearance of cipro¯oxacin was decreased and net intestinal clearance increased. 5 The speci®city of cipro¯oxacin intestinal transport appears to be di erent from P-gp as outlined by the lack of competition with spar¯oxacin, a P-gp substrate. Cipro¯oxacin intestinal elimination seems to be mediated by organic anion and/or cation transporters and a mechanism sensitive to quinidine and verapamil.

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Influence of Renal Failure on Intestinal Clearance of Ciprofloxacin in Rats

Cited by 9 publications

References 14 publications

Population pharmacokinetics and target attainment of ciprofloxacin in critically ill patients

Population pharmacokinetics and target attainment of ciprofloxacin in critically ill patients

Pharmacokinetics of Ciprofloxacin in Patients with Acute Renal Failure Undergoing Continuous Venovenous Haemofiltration: Influence of Concomitant Liver Cirrhosis

Active intestinal elimination of ciprofloxacin in rats: modulation by different substrates

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