Pharmaceutics
Physiologically Based Pharmacokinetic Modeling of Venetoclax in Pediatric Acute Myeloid Leukemia: Food Effects, Age-Related Pharmacokinetics, and Voriconazole-Mediated Drug-Drug Interactions
By Li Y, Liu M, Ling Q and 4 others.
Abstract
Background
Venetoclax (VEN), a selective B-cell lymphoma 2 inhibitor, has been increasingly used off-label in pediatric patients with hematologic malignancies. However, its pharmacokinetic characteristics in pediatric patients remain insufficiently characterized.
Methods
An adult VEN physiologically based pharmacokinetic (PBPK) model was developed and extrapolated to children using age-dependent physiological and CYP3A4 ontogeny data. The pediatric model was calibrated and evaluated using data from 76 children with AML (203 plasma concentrations) and subsequently applied to assess food effects, age-related pharmacokinetic differences, and VEN dose-reduction scenarios during VCZ co-administration. The clinical study was registered with the Chinese Clinical Trial Registry (ChiCTR1900027146 and ChiCTR2400080307).