부산대학교 도서관

IntroductionWith approximately 50% of the drugs being prescribed off-label, the pediatric population is in need for an innovative approach to establish harmonized, best evidence-based dosing guidelines. Physiologically-based pharmacokinetic (PBPK) modelling is a valuable approach to predict drug pharmacokinetics (PK) and to support dosing. As a first step to implement PBPK-informed dosing in pediatric clinical care, we aimed to identify drugs suitable to verify the PBPK approach and prioritize drugs in need of model-informed dosing.MethodsTo select a drug, it required to be listed on: 1. the Model List of Essential Medicines for Children (EMLc) of the WHO and on 2. the Dutch Pediatric Formulary (DPF). Also, a Simcyp® PBPK compound model had to be available. The level of evidence of the dosing recommendations in the DPF, the availability of pediatric pharmacokinetic data, and the opinion of clinicians on the relevance of the drug were reviewed for further prioritization.ResultsOf all drugs on the EMLc, 199 are listed in the DPF. For 76 of them, a Simcyp® compound model is available, either directly in the software, its repository, or from scientific literature. Eleven drugs have sufficient PK data to verify the PBPK modeling approach. For 48 drugs, we identify a moderate to high priority for a model-informed dose.ConclusionsThis work now provides input for the next steps which include verification of PBPK model performance in pediatrics and subsequent PBPK modelling to establish dosing guidelines. A joint effort and an internationally accessible platform are needed to share information on pediatric PBPK modelling to eventually implement model-informed doses in clinical practice.This abstract is based on research funded by the Bill & Melinda Gates Foundation