PBPK modeling for drug dosing in pediatric patients: a tutorial for a pragmatic approach in clinical care.

It is well accepted that off-label drug dosing recommendations for pediatric patients should be based on the best available evidence. However, the available traditional evidence is often low. To bridge this gap, physiologically-based pharmacokinetic (PBPK) modeling is a scientifically well-founded tool that can be used to enable model-informed dosing (MID) recommendations in children in clinical practice. In this tutorial, we provide a pragmatic, PBPK-based pediatric modeling workflow. For this approach to be successfully implemented in pediatric clinical practice, a thorough understanding of the model assumptions and limitations is required. More importantly, careful evaluation of a MID approach within the context of overall benefits and the potential risks is crucial. The tutorial is aimed to help modelers, researchers and clinicians, to effectively employ PBPK simulations to support pediatric drug dosing.