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 AUC(inf) values (at the first dose) and AUC(ss) (at the steady state) were 1060.4 microM.min (range: 511.1-1812.7) and 1092.5 microM.min (range: 539.7-1560.8) respectively. All patients had an AUC(inf) of <1500 microM.min at the first dose, and 13 of the 16 (81.3%) maintained AUC(ss) levels between 800 and 1500 microM.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.
Cho
Yo-Han
YH
Department of Internal Medicine, Konkuk University College of Medicine, Seoul, Korea.
Lim
Hyun-Ae
HA
Lee
Mark Hong
MH
Kim
Inho
I
Lee
Jong Seok
JS
Park
Seong yang
Sy
Kim
Byoung Kook
BK
Yoon
Sung-Soo
SS
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002066:Busulfan / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation; D006504:Hepatic Veno-Occlusive Disease / Q000209:etiology; D006801:Humans; D007262:Infusions, Intravenous; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy
D016179:Granulocyte Colony-Stimulating Factor; D002066:Busulfan