Pharmacokinetics and tolerability of intravenous busulfan in hematopoietic stem cell transplantation.

Intravenous (IV) busulfan has been developed to overcome variable absorption of oral busulfan and tested in several trials. We tested its pharmacological properties and tolerability in 16 Korean stem cell transplantation (SCT) patients. IV busulfan was administered at 0.8 mg/kg every six h for a total of 16 doses (days −7 to −4), which was followed by cyclophosphamide administration at 60 mg/kg every 24 h for two d (days −3 and −2). The median AUCinf values (at the first dose) and AUCss (at the steady state) were 1060.4 μM·min (range: 511.1–1812.7) and 1092.5 μM·min (range: 539.7–1560.8) respectively. All patients had an AUCinf of <1500 μM·min at the first dose, and 13 of the 16 (81.3%) maintained AUCss levels between 800 and 1500 μM·min. Thirteen of 16 patients showed successful engraftments but four patients (25%) developed hepatic VOD (two of which were fatal), three of whom had advanced disease at the time of SCT. Overall, pharmacokinetics of IV busulfan in our SCT patients appeared comparable with those observed in other study. However, hepatic VOD was a major morbidity in patients with advanced disease. [ABSTRACT FROM AUTHOR]