Model-Informed Precision Dosing of Busulfan for Children and Adults Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: A Critical Evaluation of Current PK Models and Dose Recommendations.

ABSTRACT: Busulfan is administered intravenously in conditioning regimens prior to allogeneic hematopoietic stem cell transplantation (HSCT), with model-informed precision dosing (MIPD) targeting a 4-day cumulative AUC of 80-100 mg*hour/L. Three pharmacokinetic (PK) models-Bognar, Langenhorst, and McCune-were evaluated using data with a minimum of 1 and a median of 2 PK sampling days from pediatric and adult patients at two tertiary hospitals in the Netherlands. Simulations with the best-performing model evaluated dose optimization and the role of therapeutic drug monitoring (TDM). The Bognar and Langenhorst models, with overlapping datasets (25% between models, 21% with the current), accurately described busulfan concentration-time curves in all 535 patients (0.18-72 years), especially in those > 6

SUBMITTER: Mahomedradja RF 

PROVIDER: S-EPMC12355023 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature