Physiologically Based Pharmacokinetic Modeling-Based Evaluation of Current Carbamazepine and Valproic Acid Dosing Guidelines for Pediatric Epilepsy Treatment.

ABSTRACT:

Background

Carbamazepine and valproic acid (VPA) are long-standing treatments for epilepsy in children. Interestingly, they display unique drug disposition characteristics, and maturation of drug metabolizing enzymes further complicates personalized dosing. Physiologically based pharmacokinetic (PBPK) modeling includes these mechanisms so is a promising tool to optimize dosing. Our aim was to better support pediatric drug dosing of carbamazepine and VPA.

Methods

All carbamazepine and VPA dosing simulations were conducted with Simcyp, using available carbamazepine and VPA compound models linked with adult and pediatric population models. To verify model adequacy, adult and pediatric pharmacokinetic data were retrieved from the literature to compare predicted carbamazepine and

SUBMITTER: van der Heijden JEM 

PROVIDER: S-EPMC12378131 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature