Therapeutic drug monitoring of meropenem and pharmacokinetic-pharmacodynamic target assessment in critically ill pediatric patients from a prospective observational study.

OBJECTIVES: To compare the unbound plasma meropenem concentrations at mid-dosing intervals (Cmid, 50%fT), end-dosing intervals (Ctrough, 100%fT), and proportions of patients achieving 50%fT and 100%fT above minimum inhibitory concentration (MIC) (50%fT>MIC and 100%fT>MIC) between extended infusion (EI) and intermittent bolus (IB) administration in a therapeutic drug monitoring (TDM) program in children. METHODS: A prospective observational study was conducted in children aged 1 month to 18 years receiving meropenem every 8 hours by either EI or IB. Meropenem Cmid, Ctrough, and proportions of patients achieving 50%fT>MIC and 100%fT>MIC were compared. RESULTS: TDM data from 72 patients with a median age (interquartile range [IQR]) of 12 months (3-37) were used. Meropenem dose was 120 and 60 mg/kg/day in EI and IB groups, respectively. Geometric mean (95% confidence interval [CI]) Cmid of EI versus IB was 17.3 mg/L (13.7-21.8) versus 3.4 mg/L (1.7-6.7) (P <0.001). Geometric mean (95% CI) Ctrough of EI versus IB was 2.3 mg/L (1.6-3.4) versus 0.8 mg/L (0.4-1.5) (P=0.005). Greater proportions of patients achieving 50%fT>MIC and 100%fT>MIC were observed in the EI group. CONCLUSIONS: A meropenem dose of 20 mg/kg/dose given by IB should not be used in critically ill children, even if they are not suspected of having a central nervous system infection. A dose of 40 mg/kg/dose given by EI resulted in higher Cmid, Ctrough, and proportions of patients achieving 50%fT>MIC and 100%fT>MIC.

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 (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.