• 학회명 : 대한조혈모세포 이식학회 동계학술대회
• 기간 : 2006.2.10~11
• 장소 : 무주리조트
• 발표자 : Seong-Gil Ryu³, Je-Hwan Lee¹, Seong-Jun Choi¹, Jung-Hee Lee¹, Young-Shin Lee¹, Miee Seol¹, Eun-Hye Hur¹, Ae-Kyoung Hwang², Kyun-Seop Bae², Gyu-Jeong Noh², Kyoo-Hyung Lee¹

             Departments of Internal Medicine¹, and Clinical Pharmacology², and Pharmacy³,

             Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

• 발표초록 :

  Although most experience with intravenous busulfan has been with the traditional 4-times-daily dosing, several investigators have recently reported the clinical and pharmacologic experience using one-daily or twice-daily intravenous busulfan as a conditioning therapy for hematopoietic cell transplantation (HCT). If equally effective, daily dosing of busulfan would be more convenient than divided dosing. We performed a prospective randomized trial of 4-times-daily vs. once-daily dosing of intravenous busulfan as a conditioning therapy for HCT and pharmacokinetic characteristics of intravenous busulfan in each arm were compared. The influence of glutathione-S-transferase (GST) polymorphism on pharmacokinetics was also analyzed. All of 60 patients, who underwent HCT, were randomized to receive intravenous busulfan either as 0.8 mg/kg over 2 hours 4 times a day or 3.2 mg/kg over 3 hours once a day. Limited sampling strategy was used for pharmacokinetic studies, which were done for the first busulfan dosing. Blood samples were drawn in 5-time points including peak and trough level and were assayed by HPLC with Mass spectrophotometer/Mass spectrophotometer (LC-MS/MS, Agilent technologies 1100 series). The pharmacokinetic parameters were calculated from the model-derived parameters using NONMEM 5 level 1.1. The complete PK data were obtained from all 60 patients. The elimination half-life (mean ± SD) was 2.75 ± 0.22 hr and 2.83 ± 0.21 hr in 4-times-daily group and once-daily group, respectively (p=0.304), AUC was 1983.36 ± 544.43μM/min and 8556.86 ± 2452.07μM/min (p=0.000), estimated AUC was 7933.43 ± 2177.71 μM/min/mg, 8556.86 ± 2452.07 μM/min/mg (p=0.367), and clearance was 2.05 ± 0.36 ml/min/kg and 1.91 ± 0.31 ml/min/kg (p=0.133). In once-daily group, GST T1-null polymorphism was significantly associated with lower Vd and Cl, higher AUC (p <0.05). Our study showed that the pharmacokinetic characteristics of once-daily busulfan dosing offered a comparable profile to traditional 4-times-daily dosing.