Physiologically-based pharmacokinetic models versus allometric scaling for prediction of tyrosine-kinase inhibitor exposure from adults to children.

ABSTRACT:

Purpose

Model-based methods can predict pediatric exposure and support initial dose selection. The aim of this study was to evaluate the performance of allometric scaling of population pharmacokinetic (popPK) versus physiologically based pharmacokinetic (PBPK) models in predicting the exposure of tyrosine kinase inhibitors (TKIs) for pediatric patients (≥ 2 years), based on adult data. The drugs imatinib, sunitinib and pazopanib were selected as case studies due to their complex PK profiles including high inter-patient variability, active metabolites, time-varying clearances and non-linear absorption.

Methods

Pediatric concentration measurements and adult popPK models were derived from the literature. Adult PBPK models were generated in PK-Sim® using available physicochemica

SUBMITTER: Centanni M 

PROVIDER: S-EPMC11390758 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature