Population pharmacokinetic model for meropenem in pediatric patients: a systematic review

The pharmacokinetics of meropenem in pediatric patients have large interindividual variability. Model-informed precision dosing (MIPD) is a promising way to ensure optimal exposure but relies on a population pharmacokinetic (PPK) model. This review systemically synthesized the available PPK model for meropenem in pediatric patients to facilitate MIPD in these patients.

Four electronic databases were searched for eligible studies that reported the use of the meropenem PPK model for pediatric patients. The study design information, patient characteristic demography, PPK modeling strategy and final PPK parameter estimates were extracted and reviewed.

Twenty studies published from 2006 to 2025 were included in the analysis. Fourteen studies had prospective designs, and four studies were international multicenter studies. Seven studies applied an intensive sampling strategy. Pediatric patients with various characteristics were included, and most had severe infections or were admitted to the ICU. Four studies focused on patients with organ support, mainly renal replacement and extracorporeal membrane oxygenation. The sample sizes were usually small (sample sizes no more than 50). Fourteen studies ultimately obtained the 2-CMT model, and the remaining studies used the 1-CMT model, except for one 3-CMT model. Body weight, age and renal function indicators were the most common covariates. The typical CL values ranged from 0.50-13.22 L/h or 0.122-0.526 L/h/kg. The Vcs for the 2-CMT models ranged from 0.969-21.4 L or 0.272-0.57 L/kg. Most models underwent internal validation, but only one study performed external validation.

This study successfully integrated the current meropenem PPK models for pediatric patients, which would benefit the clinical application of MIPD. Clinicians should select appropriate models on the basis of patient characteristics carefully, and therapeutic drug monitoring is important at the current stage. External validation and well-designed studies on specific subpopulations, such as patients with organ support, neonates, and specific disease status, are needed.

PROSPERO, identifier (CRD420261481301).