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Pharmacokinetics of intravenous busulfan and evaluation of the bioavailability of the oral formulation in conditioning for haematopoietic stem cell transplantation.

Authors
Type
Published Article
Journal
Bone Marrow Transplantation
0268-3369
Publisher
Nature Publishing Group
Publication Date
Volume
22
Issue
3
Pages
241–244
Identifiers
PMID: 9720736
Source
Medline
License
Unknown

Abstract

Busulfan (BU) is included in many conditioning protocols for haematopoietic stem cell transplantation (HSCT). Pharmacokinetic parameters in individual patients have been related to short-term toxicity and risk of relapse after HSCT. In a series of 11 patients receiving the usual 16 x 1 mg/kg schedule over 4 days, we investigated the pharmacokinetics of replacing one dose with an intravenous formulation (BU in DMSO) which we had previously investigated in dogs. A dose of 0.5-0.6 mg/kg was used. No acute side-effects of BU/DMSO infusions administered over 1 h were observed. Bioavailability of BU powder capsules was on average 70% (range, 44-94%). Interindividual variability of the resulting AUC after intravenous doses was still substantial. Further studies are under way to define the possible role of BU/DMSO infusions in conditioning before HSCT.

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