From PICU to NICU: Extrapolating Meropenem Exposure From Pediatric to Neonatal Intensive Care Patients.

We previously developed a population pharmacokinetic (PopPK) model for meropenem in pediatric intensive care unit patients accounting for effect of body size, maturation, and kidney function on clearance. This study aimed to extrapolate meropenem exposure to neonates and young infants using the pediatric PopPK model and to validate the predictions using external data. An independent dataset was obtained from the regulations.gov website, which included 176 neonates and young infants (up to 3 months old) with a total of 767 plasma meropenem concentrations. After normalizing the estimated glomerular filtration rate (eGFR) using a maturation factor, the PopPK model was applied to this dataset and the concordance between the model predictions and observed concentrations was visually assessed using goodness-of-fit (GOF) plots and prediction-corrected visual predictive check. Median prediction error (MDPE) evaluated bias and median absolute prediction error (MDAPE) evaluated precision of the predictions. GOF plots indicated no apparent bias or model misspecification. Individual-level predictions showed an MDPE of 1% and an MDAPE of 18.3%, both within commonly accepted thresholds for bias (<±20%-30%) and precision (<30%-35%), respectively. The findings support the model's application for simulations when neonatal eGFR is normalized using a maturation factor and for model-informed precision dosing in clinical practice for neonates and infants.