Use of an Oral Busulfan Test Dose in Patients Undergoing Hematopoietic Stem Cell Transplantation Treated With or Without Fludarabine

This study investigated the importance of an oral test dose for busulfan (BU) dose adjustment before a conditioning regimen for hematopoietic stem-cell transplantation (HSCT) and the effect of fludarabine (FLU) on the oral BU pharmacokinetics evaluated after the fifth treatment dose (first BU dose on day 2 of treatment). Twenty-eight patients treated with oral BU (1 mg/kg every 6 hours for 4 days) were divided into 2 groups according to the concomitant administration of FLU (n = 15; 30 mg/m(2) for 5 days) or subsequent administration of cyclophosphamide (CY) (n = 13; 60 mg/kg for 2 days). On the day prior to the beginning of the conditioning regimen, blood samples were collected (0-6 hours) after administration of an oral BU test dose of 0.25 mg/kg. Busulfan was quantified in plasma samples by LC-MS/MS, and the pharmacokinetic parameters were calculated using WinNonlin software. Blood samples were collected between the fifth and sixth treatment dose to confirm the mean plasma steady-state concentration (C-ss) of BU. The AUC(0-6) and apparent clearance of BU did not differ (P < .05) between the groups receiving FLU and CY. In 81% of the patients who received BU doses adjusted based on the test dose (n = 21), the C-ss was within the target range of 600-900 ng/mL. No association was observed between BU AUC(0-6) and clinical outcome in the study group (n = 28). The results suggest that in concomitant administration of FLU and BU during conditioning regimens for HSCT, changes in BU dose should be considered only after the administration of the fifth BU dose.