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

What is already known about this subject • There is only one published study of the population pharmacokinetics of ceftazidime in burn patients. Only one covariate (plasma creatinine concentration) was found to contribute to the interindividual variability in the disposition of the drug. What this s...

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Bibliographic Details
Published in:British journal of clinical pharmacology 2007-07, Vol.64 (1), p.27-35
Main Authors: Conil, Jean Marie, Georges, Bernard, Lavit, Michel, Laguerre, Jacky, Samii, Kamram, Houin, Georges, Saivin, Sylvie
Format: Article
Language:English
Subjects:
Adult
Aged
Anti-Bacterial Agents - blood
Anti-Bacterial Agents - pharmacokinetics
Biological and medical sciences
burn patients
Burns
Burns - metabolism
ceftazidime
Ceftazidime - blood
Ceftazidime - pharmacokinetics
Female
Glomerular Filtration Rate - physiology
Humans
Male
Medical sciences
Middle Aged
Models, Biological
Pharmacokinetics
Pharmacology. Drug treatments
population pharmacokinetics
Respiration, Artificial
Sex Factors
Traumas. Diseases due to physical agents
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Summary:What is already known about this subject • There is only one published study of the population pharmacokinetics of ceftazidime in burn patients. Only one covariate (plasma creatinine concentration) was found to contribute to the interindividual variability in the disposition of the drug. What this study adds • Three other covariables (creatinine clearance, mechanical ventilation and gender) have been added to a two compartment pharmacokinetic model incorporating multiplicative error, and these are able to explain much of the interindividual variability in ceftazidime disposition in burn patients. 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: 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 −1for 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.
ISSN:0306-5251
1365-2125
DOI:10.1111/j.1365-2125.2007.02857.x