Comparison of equal doses of continuous venovenous haemofiltration and haemodiafiltration on ciprofloxacin population pharmacokinetics in critically ill patients

Roger, Claire, Wallis, Steven C., Louart, Benjamin, Lefrant, Jean-Yves, Lipman, Jeffrey, Muller, Laurent and Roberts, Jason A. (2016) Comparison of equal doses of continuous venovenous haemofiltration and haemodiafiltration on ciprofloxacin population pharmacokinetics in critically ill patients. Journal of Antimicrobial Chemotherapy, 71 6: 1643-1650. doi:10.1093/jac/dkw043


Author Roger, Claire
Wallis, Steven C.
Louart, Benjamin
Lefrant, Jean-Yves
Lipman, Jeffrey
Muller, Laurent
Roberts, Jason A.
Title Comparison of equal doses of continuous venovenous haemofiltration and haemodiafiltration on ciprofloxacin population pharmacokinetics in critically ill patients
Journal name Journal of Antimicrobial Chemotherapy   Check publisher's open access policy
ISSN 1460-2091
0305-7453
Publication date 2016-06
Year available 2016
Sub-type Article (original research)
DOI 10.1093/jac/dkw043
Open Access Status Not Open Access
Volume 71
Issue 6
Start page 1643
End page 1650
Total pages 8
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2017
Language eng
Formatted abstract
Objectives: Whilst commonly performed in ICUs, renal replacement therapies (RRTs) differ in their solute clearances. There is a paucity of data on ciprofloxacin clearances in different RRT techniques. The aim of this study was to compare the population pharmacokinetics of ciprofloxacin during equal doses of continuous venovenous haemofiltration (CVVHF) and continuous venovenous haemodiafiltration (CVVHDF) in septic patients.

Methods: Patients receiving 400 mg of ciprofloxacin intravenously 8 or 12 hourly and undergoing either CVVHF or CVVHDF were eligible. Up to 10 blood sampleswere collected over one dosing interval and analysed by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo simulation was undertaken using Pmetrics.

Results: Eighteen sampling intervals were included (8 CVVHDFand 10 CVVHF) from 11 patients (6 patients having sampling during both RRT modes). A two-compartment linear model best described the data. Increasing patient weight was the only covariate associated with increasing drug clearance. The mean (SD) parameter estimates were: clearance, 10.7 (5.3) L/h; volume of distribution of the central compartment, 21.3 (11.3) L; rate constant for drug distribution from the central compartment to the peripheral compartment, 10.9 (4.3) L/h; and rate constant for drug distribution from the peripheral compartment to the central compartment, 2.3 (1.8) L/h. After accounting for patient weight, the mean ciprofloxacin clearance was not statistically different between CVVHF and CVVHDF [11.8 (9.9) and 10.3 (7.4) L/h, respectively, P=0.43].

Conclusions: The present study indicates a high pharmacokinetic variability of ciprofloxacin during CVVHF and CVVHDF with no significant differences in clearance apparent. Based on patient weight, higher ciprofloxacin dosing regimens should be used in critically ill patients when difficult-to-treat pathogens are suspected.
Keyword Renal replacement therapies
Comparison
Ciprofloxacin clearances
Continuous venovenous haemofiltration
Continuous venovenous haemodiafiltration
Septic patients
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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