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Ciprofloxacin use in critically ill patients: pharmacokinetic and pharmacodynamic approaches.

Abstract
The objective of this study was to evaluate the properties of ciprofloxacin in intensive care patients using a population approach. Seventy patients received ciprofloxacin. On Day 1, three to eight blood samples were taken over a 12-h period. Peak drug concentration (Cmax) and 24-h area under the concentration-time curve (AUC) were compared with the French breakpoint defining antibiotic susceptibility. A population pharmacokinetic modelling approach was then carried out. A two-compartment open model with a proportional error model best fitted the data. A relationship between the elimination constant rate and the Cockcroft creatinine clearance was found. Ciprofloxacin clearance was 13.6+/-5.8L/h, the volume of distribution was 62.0+/-10.7 L and the ciprofloxacin half-life was 3.7+/-1.8h. When the minimum inhibitory concentration (MIC) was equal to 1mg/L the inhibitory ratio (IR) was > or = 8 in only 10.8% of cases, and the AUC/MIC ratio (AUIC) was 42.0+/-36. In conclusion, this study highlights that the Cockcroft clearance significantly influences ciprofloxacin elimination. Target plasma concentrations for ciprofloxacin, the IR and AUIC were rarely reached with a standard dosing regimen. In critically ill patients, the observed pharmacokinetic variability is mainly responsible for the overly frequent low concentrations of ciprofloxacin, emphasising the need for therapeutic monitoring.
AuthorsJean-Marie Conil, Bernard Georges, Anne de Lussy, Dalia Khachman, Thierry Seguin, Stéphanie Ruiz, Pierre Cougot, Olivier Fourcade, Georges Houin, Sylvie Saivin
JournalInternational journal of antimicrobial agents (Int J Antimicrob Agents) Vol. 32 Issue 6 Pg. 505-10 (Dec 2008) ISSN: 0924-8579 [Print] Netherlands
PMID18768301 (Publication Type: Journal Article)
Chemical References
  • Anti-Bacterial Agents
  • Ciprofloxacin
Topics
  • Aged
  • Algorithms
  • Anti-Bacterial Agents (pharmacokinetics, therapeutic use)
  • Bacteria (drug effects)
  • Ciprofloxacin (pharmacokinetics, therapeutic use)
  • Critical Illness
  • Female
  • Half-Life
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged

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