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Pharmacokinetics and tolerability of intravenous busulfan in hematopoietic stem cell transplantation
Author(s) -
Cho YoHan,
Lim HyunAe,
Lee Mark Hong,
Kim Inho,
Lee Jong Seok,
Park Seong yang,
Kim Byoung Kook,
Yoon SungSoo
Publication year - 2007
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/j.1399-0012.2007.00664.x
Subject(s) - busulfan , medicine , tolerability , pharmacokinetics , transplantation , hematopoietic stem cell transplantation , cyclophosphamide , gastroenterology , pharmacology , chemotherapy , surgery , adverse effect
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 AUC inf values (at the first dose) and AUC ss (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 AUC inf of <1500 μM·min at the first dose, and 13 of the 16 (81.3%) maintained AUC ss 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.