A population pharmacokinetic approach to ceftazidime use in burn patients: influence of glomerular filtration, gender and mechanical ventilation

Aims The aim of this study was to evaluate the disposition of ceftazidime in burn patients using a population pharmacokinetic approach, and to identify the clinical and biological parameters influencing its pharmacokinetics. Methods The development of the pharmacokinetic model was based on 237 serum ceftazidime concentrations from 50 burn patients. The determination of the pharmacokinetic parameters and the selection of covariates were performed using a nonlinear mixed-effect modelling method. Results A two-compartment model with first order elimination incorporating a proportional error model best fitted the data. Ceftazidime clearance (CL, l h(-1)) was significantly correlated with creatinine clearance (CLCR), and the distribution volume of the peripheral compartment (V2, l) was correlated with gender, mechanical ventilation and the CLCR. The final model was defined by the following equations: CL = 1 08 + 0.0536 x CLCR Q (intercompartmental clearance) = 6.881 1h(-1) V1 (distribution volume of the central compartment) - 18.81 V2 = 2.69 x (1 + 1.43 x SEX) x (1 + 2.44 x VENT) x (1 + 0.00414 x CLCR) Ceftazidime clearance was 6.1 and 5.7 l h(-1) for mechanically ventilated males and females, respectively, and 7.2 and 6.6 l h(-1) for nonventilated patients. The total volume of distribution was 31.6 and 49.4 l for mechanically ventilated males and females, respectively, and 22.8 and 28.1 l h (-1)for nonventilated patients. Conclusions We have shown that gender, mechanical ventilation and CLCR significantly influence the disposition of ceftazidime in burn patients. Interindividual variability in the pharmacokinetics of ceftazidime was significant and emphasizes the need for therapeutic monitoring.