Ciprofloxacin use in critically ill patients: pharmacokinetic and pharmacodynamic approaches

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 (C-max) and 24-h area under the concentration-time curve (AUC) were compared with the French breakpoint de. ning 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 +/- 5.8 L/h, the volume of distribution was 62.0 +/- 10.7 L and the ciprofloxacin half-life was 3.7 +/- 1.8 h. When the minimum inhibitory concentration (MIC) was equal to 1 mg/L the inhibitory ratio (IR) was >= 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. (C) 2008 Elsevier B. V. and the International Society of Chemotherapy. All rights reserved.