Physiologically-Based Pharmacokinetic Modeling of Total and Unbound Valproic Acid to Evaluate Dosing in Children With and Without Hypoalbuminemia.

ABSTRACT:

Background and objective

Valproic acid (VPA) demonstrates nonlinear pharmacokinetics (PK) due to a capacity-limited protein binding, which has potential implications on its total and unbound plasma concentrations, especially during hypoalbuminemia. A physiologically based pharmacokinetic (PBPK) model was developed to assess the nonlinear dose-exposure relationship of VPA with special emphasis on pediatric patients with hypoalbuminemia.

Methods

A PBPK model was first developed and evaluated in adults using PK-Sim^® and MoBi^® (v.11) and the scaled to children 1 year and older. The capacity-limited protein binding was characterized by second-order kinetics between VPA and albumin with a 2:1 molar ratio. All drug-specific parameters were informed by literatu

SUBMITTER: Karatza E 

PROVIDER: S-EPMC11521762 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature