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. 2007 Jul;64(1):27-35.
doi: 10.1111/j.1365-2125.2007.02857.x. Epub 2007 Feb 23.

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

Jean Marie Conil  1 , Bernard Georges, Michel Lavit, Jacky Laguerre, Kamram Samii, Georges Houin, Sylvie Saivin
Affiliations

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

Jean Marie Conil et al. Br J Clin Pharmacol. 2007 Jul.

Abstract

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 (CL(CR)), and the distribution volume of the peripheral compartment (V2, l) was correlated with gender, mechanical ventilation and the CL(CR). The final model was defined by the following equations: 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 CL(CR) 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.

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Figures

Figure 1
Figure 1
Ceftazidime concentrations vs. time in 50 burn patients. Concentrations were normalized to the mean daily dose per kg
Figure 2
Figure 2
Correlations between the predicted concentrations starting from the population (PRED) (A) and the individual predicted concentrations (IPRED) (B) and the observed concentrations (DV) based on a two-compartment model
Figure 3
Figure 3
Distributions of the residues (A) and weighted residues (B) according to the predicted concentrations (PRED) based on a two-compartmental model incorporating a proportional error model
See this image and copyright information in PMC

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