title: Comparison of equal doses of continuous venovenous haemofiltration and haemodiafiltration on ciprofloxacin population pharmacokinetics in critically ill patients.
abstract: 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.
  
  
  
  Patients receiving 400 mg of ciprofloxacin intravenously 8 or 12 hourly and undergoing either CVVHF or CVVHDF were eligible. Up to 10 blood samples were collected over one dosing interval and analysed by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo simulation was undertaken using Pmetrics.
  
  
  
  Eighteen sampling intervals were included (8 CVVHDF and 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].
  
  
  
  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.
authors.affiliation: Service des réanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Nîmes, France Equipe d'Accueil 2992, Faculté de Médecine de Nîmes, Université de Montpellier, Nimes, France Burns, Trauma, and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia claire.roger@chu-nimes.fr.
authors.forename: Claire
authors.initials: C
authors.lastname: Roger
authors.affiliation: Burns, Trauma, and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Wallis
authors.affiliation: Service des réanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Nîmes, France Equipe d'Accueil 2992, Faculté de Médecine de Nîmes, Université de Montpellier, Nimes, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Louart
authors.affiliation: Service des réanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Nîmes, France Equipe d'Accueil 2992, Faculté de Médecine de Nîmes, Université de Montpellier, Nimes, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Lefrant
authors.affiliation: Burns, Trauma, and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia Department of Intensive Care Medicine, Royal Brisbane and Womens' Hospital, Brisbane, Queensland, Australia.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.affiliation: Service des réanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Nîmes, France Equipe d'Accueil 2992, Faculté de Médecine de Nîmes, Université de Montpellier, Nimes, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Muller
authors.affiliation: Burns, Trauma, and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia Department of Intensive Care Medicine, Royal Brisbane and Womens' Hospital, Brisbane, Queensland, Australia Pharmacy Department, Royal Brisbane and Womens' Hospital, Brisbane, Queensland, Australia.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects / Q000472:pathogenicity; D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016638:Critical Illness; D004926:Escherichia coli / Q000187:drug effects / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology; D005260:Female; D017583:Hemodiafiltration; D006440:Hemofiltration; D006801:Humans; D007262:Infusions, Intravenous; D007362:Intensive Care Units / Q000706:statistics & numerical data*; D007710:Klebsiella Infections / Q000188:drug therapy / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000472:pathogenicity; D008297:Male; D008875:Middle Aged; D009010:Monte Carlo Method; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000472:pathogenicity; D017582:Renal Replacement Therapy / Q000379:methods*; D018805:Sepsis / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin