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Population pharmacokinetics of imipenem in burn patients
Author(s) -
Dailly Eric,
Kergueris Marie France,
Pannier Michel,
Jolliet Pascale,
Bourin Michel
Publication year - 2003
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1046/j.1472-8206.2003.00190.x
Subject(s) - pharmacokinetics , imipenem , renal function , volume of distribution , medicine , population , creatinine , therapeutic drug monitoring , pharmacology , urology , chemistry , antibiotics , biochemistry , environmental health , antibiotic resistance
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.