Population pharmacokinetics of meropenem in critically ill infant patients

Abstract

Background: Population pharmacokinetic analysis in critically ill infants remains a challenge for lack of information. Objectives: To determine the population pharmacokinetic parameters of meropenem and evaluate the covariates affecting population pharmacokinetic parameters. Methods: A prospective study was conducted on 35 patients. A total of 160 blood samples were collected and determined free of 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. Results: A one-compartment model with first-order elimination showed the best fit to the data.The typical clearance (CL) values 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% f T>MIC but not enough if a more aggressive target of 80% f T>MIC at MIC value of ≥ 16 µg/mL is desired. Conclusions: This population pharmacokinetic model could be used for suggesting individualized meropenem dosage regimens in critically ill infants.

Keywords

• Meropenem
• Population pharmacokinetics
• Critically ill
• Infants