4.0 Article

Is Busulfan Clearance Different in Patients With Sickle Cell Disease? Let's Clear Up That Case With Some Controls

Journal

JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
Volume 43, Issue 6, Pages E867-E872

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MPH.0000000000002106

Keywords

busulfan; pharmacokinetics; sickle cell disease; hematopoietic stem cell

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This study found that SCD does not significantly affect the metabolic clearance rate of the first dose of busulfan, regardless of genetic or anthropometric factors considered.
In busulfan-based conditioning regimen for hematopoietic stem cell transplantation in children, accurate a priori determination of the first dose is important because of its narrow therapeutic window. Sickle cell disease (SCD) influences pharmacokinetics of the commonly used drugs by affecting organs responsible for drug metabolism and elimination. This pharmacokinetics study assesses the influence of SCD on the metabolic pathway of busulfan that is mainly metabolized in the liver. In this retrospective cross-sectional case-control study, 16 patients with SCD were matched to 50 patients without SCD on known busulfan clearance's covariates (glutathione-S-transferase alpha1 polymorphisms, age, weight). Clearance of the first dose of busulfan was not significantly different independently of genetic or anthropometric factors in patients with or without SCD.

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