Population pharmacokinetics of imipenem in burn patients.
The interindividual variability of imipenem pharmacokinetic parameters in burn patients suggest that these parameters have to be estimated with a large number of patients. The aim of this study is (i) to estimate these parameters with a population pharmacokinetic approach, and (ii) to test the influence of factors on pharmacokinetics parameters. Data are provided by therapeutic drug monitoring (n = 47,118 samples) and analysed by a nonlinear mixed effect modelling method. Among the tested covariates (age, gender, body weight, height, size of burn and creatinine plasma level) creatinine plasma level affects imipenem pharmacokinetic parameters substantially. The best fit is obtained with a two-compartment model integrating a linear-inverse relationship between imipenem clearance and creatinine plasma level. The estimates of imipenem clearance (16.37 +/- 0.204 L/h) and of the distribution volume of the central compartment (0.376 +/- 0.039 L/kg) are higher in the population of burn patients than the estimates in healthy subjects. This result is connected with high values of glomerule filtration rate and confirms the interest of therapeutic drug monitoring of imipenem in burn patients and particularly for patients with extreme values of creatinine clearance.
Dailly
Eric
E
Clinical Pharmacology Department, Hôtel Dieu Hospital, Nantes, France. eric.dailly@chu-nantes.fr
Kergueris
Marie France
MF
Pannier
Michel
M
Jolliet
Pascale
P
Bourin
Michel
M
D002056:Burns / Q000188:drug therapy* / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007275:Injections, Intravenous; D008657:Metabolic Clearance Rate; D012189:Retrospective Studies
D015378:Imipenem; D003404:Creatinine