PII-069 - EXTERNAL EVALUATION OF A POPULATION PHARMACOKINETICS MODEL OF CRITICALLY ILL PEDIATRIC PATIENTS RECEIVING MEROPENEM

L. Cheng¹, P. Cojutti², F. Pea³, S. Tang-Girdwood⁴, R. Morales Jr.⁴; ¹Emory College, Dayton, OH, United States, ²IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy, ³University of Bologna, Bologna, Italy, ⁴Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of America.

Background: Meropenem poses significant dosing challenges for critically ill patients due to variable pharmacokinetics. We previously developed a PopPK model using data from pediatric intensive care unit (PICU) patients receiving meropenem as an intermittent infusion. We aim to evaluate whether this model accurately predicts steady-state concentrations for patients receiving continuous infusions so it can be effectively used for individual dosing adjustments in clinical practice.

Methods: Clinical data and steady state meropenem concentrations were obtained from PICU patients receiving meropenem as continuous infusions. The concordance between the model predictions and observed concentrations was visually assessed using goodness of fit (GOF) plots. Median prediction error (MDPE) evaluated bias; median absolute prediction error (MDAPE) and root mean square error (RMSE) evaluated precision.

Results: The external dataset included 57 patients with median age of 1.9 years (range 1 month to 18 years old), receiving 30-60 mg/kg/day of meropenem with median eGFR of 80 mL/min/1.73 m2 (range 46 -150). The distributions of prediction errors are shown in Figure 1. Error metrics for individual predictions were -2.8% MDPE, 19.3% MDAPE, and 2% RMSE, all of which fall within the commonly acceptable thresholds for bias (< ±20–30%) and precision ( < 30–35%). Error metrics for population predictions were -3.5% MDPE, 32% MDAPE, and 2.3% RMSE. In GOF plots, there was no apparent bias in the population and individual predictions.

Conclusion: Our PopPK model demonstrates strong predictive performance for critically ill pediatric patients receiving meropenem as continuous infusion. This model can be used in the PICU for model-informed precision dosing, increasing probability for patients receiving continuous infusions to reach target attainment and reducing risk for treatment failure.