Population pharmacokinetics and pharmacodynamics of meropenem in Japanese pediatric patients

The aims of this study were to develop a population pharmacokinetic model for meropenem in Japanese pediatric patients, and to use this model to assess the pharmacodynamics of meropenem regimens against common bacterial populations. Pharmacokinetic data were pooled from nine separate studies (229 plasma samples and 61 urine samples from 40 infected children), modeled using the NONMEM program, and used for a pharmacodynamic simulation to estimate the probabilities of attaining the bactericidal target (40% of the time above the MIC for the bacterium). In the final population pharmacokinetic model, body weight (BW, kg) was the most significant covariate: Cl_r (l/h) = 0.254 × BW, Cl_nr (l/h) = 3.45, V _c (l) = 0.272 × BW, Q (l/h) = 1.65, and V _p (l) = 0.228 × BW, where Cl_r and Cl_nr are the renal and non-renal clearances, V _p and V _c are the volumes of distribution of the central and peripheral compartments, and Q is the intercompartmental (central–peripheral) clearance. In most typical patients (BW = 10, 20, and 30 kg), the approved regimens of 10–40 mg/kg, three times a day (0.5-h infusions), achieved a target attainment probability of >80% against Escherichia coli, Streptococcus pneumoniae, methicillin-susceptible Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa isolates. The results of this study provide a better understanding of the pharmacokinetics and pharmacodynamics of meropenem in Japanese pediatric patients.