Semi-mechanistic population pharmacokinetic model incorporating glutathione S-transferase activity for personalized busulfan dosing in pediatric allogeneic hematopoietic cell transplantation.

ABSTRACT:

Background

Busulfan is known for its high inter- and intra-individual pharmacokinetics/pharmacodynamics (PK/PD) variability, especially in children. Therefore, we aimed to identify factors affecting PK variability of busulfan in pediatric allogeneic hematopoietic cell transplantation (HCT) recipients and investigate the effect of glutathione S-transferase (GST) activity on busulfan metabolism using a semi-mechanistic population PK model.

Methods

Overall, 636 whole-blood busulfan concentrations from 65 pediatric HCT recipients were analyzed using nonlinear mixed-effects modeling. A semi-mechanistic population PK model was developed to describe busulfan metabolism in response to glutathione (GSH) depletion. The effects of potential covariates were selected based on previous st

SUBMITTER: Cao D 

PROVIDER: S-EPMC12426406 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature