Population pharmacokinetics of meropenem in critically ill infant patients

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 (V-d) 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 V-d 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 mu g/mL is desired. Conclusions: This population pharmacokinetic model could be used for suggesting individualized meropenem dosage regimens in critically ill infants. (C) 2021 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

Automated summary

By conducting a prospective study on 35 patients, population pharmacokinetic parameters of meropenem were determined, with factors such as weight and creatinine clearance influencing its clearance and volume of distribution. Model evaluation results indicated the robustness and good predictability of the final model.