Busulfan in hematopoietic stem cell transplant setting.
This paper focuses primarily on the data published in the last decade about the pharmacokinetics and pharmacodynamics of oral and intravenous (i.v.) busulfan, therapeutic drug monitoring and clinical outcome in hematopoietic stem cell transplant (HCT) patients. Busulfan is commonly used in HCT as it is toxic to the marrow. Busulfan is available as oral or i.v. formulation. The most common significant toxicity of busulfan is sinusoidal obstruction syndrome. Even with the introduction of i.v. busulfan, variability in the systemic concentrations of busulfan after weight-based dosing and the association between busulfan plasma exposure and outcome in HCT patients have led to the continued use of therapeutic drug monitoring of busulfan. New strategies for personalizing busulfan dosing are being studied to maximize the use of busulfan for optimal disease control with the least toxicity to HCT patients. One such strategy currently being evaluated is if busulfan clearance can be accurately predicted by genetic polymorphism of glutathione S-transferase (GST), with the currently available data suggesting that GST polymorphisms cannot be used to personalize busulfan dosing.
McCune
Jeannine S
JS
University of Washington School of Medicine, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue, P.O. Box 19024, Mailstop G7-405, Seattle, WA 98109-1024, USA.
Holmberg
Leona A
LA
D000328:Adult; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D010597:Pharmacogenetics
D007166:Immunosuppressive Agents; D002066:Busulfan