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

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 × 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.