Population pharmacokinetics of meropenem in critically ill infant patients.

Abstract

BACKGROUND\nPopulation pharmacokinetic analysis in critically ill infants remains a challenge and lacks information.\n\n\nOBJECTIVES\nTo determine the population pharmacokinetic parameters of meropenem and evaluate the covariates affecting population pharmacokinetic parameters.\n\n\nMETHODS\nA prospective study was conducted in 35 patients. A total of 160 blood samples were collected and determined free drug concentrations of meropenem. Population pharmacokinetic data were analyzed using NONMEM software. Internal validation methods, including bootstrapping and prediction-corrected visual predictive checks, were applied to evaluate the robustness and predictive power of the final model.\n\n\nRESULTS\nA one-compartment model with first-order elimination showed the best fit to the data. The typical values of clearance (CL) and volume of distribution (Vd) were 1.33 L/h and 2.27 L, respectively. Weight and creatinine clearance were influential covariates for CL, while weight was a significant covariate for Vd of meropenem. The model evaluation results suggested robustness and good predictability of the final model. The standard dosage regimens of meropenem achieved 40%\xa0f\xa0T>MIC but not enough if a more aggressive target of 80%\xa0f\xa0T>MIC at MIC value of ≥ 16 µg/mL.\n\n\nCONCLUSIONS\nThis population pharmacokinetic model could be used for suggesting the individualized meropenem dosage regimens in critically ill infants.