Ryu Seong-Gil, Lee Je-Hwan, Choi Seong-Jun, Lee Jung-Hee, Lee Young-Shin, Seol Miee, Hur Eun-Hye, Lee Soo Han, Bae Kyun Seop, Noh Gyu Jeong, Lee Moo-Song, Yun Sung-Cheol, Han Sang Beom, Lee Kyoo-Hyung
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Biol Blood Marrow Transplant. 2007 Sep;13(9):1095-105. doi: 10.1016/j.bbmt.2007.06.005.
Sixty patients were randomized to receive intravenous busulfan (iBU) either as 0.8 mg/kg, over 2 hours 4 times a day (BU4 arm) or 3.2 mg/kg, over 3 hours once a day (BU1 arm) in conditioning therapy for hematopoietic cell transplantation. The complete pharmacokinetic parameters for the first busulfan dose were obtained from all patients and were comparable between the 2 arms: for the BU4 and BU1 groups, elimination half-life (mean+/-SD) was 2.75+/-0.22 versus 2.83+/-0.21 hours, estimated daily AUC was 6058.0+/-1091.9 versus 6475.5+/-1099.4 microM.min per day, and clearance was 2.05+/-0.36 versus 1.91+/-0.31 mL/min/kg, respectively. Times to engraftment after transplantation were similar between the 2 arms. No significant differences were evident in the occurrence of acute graft-versus-host disease (aGVHD) and hepatic veno-occlusion disease (VOD). Moreover, other toxicities observed within 100 days after transplantation were not significantly different between the 2 arms. The cumulative incidence of nonrelapse mortality was 20.8% in BU4 arm and 13.3% in BU1 arm. In conclusion, our randomized study demonstrates that the pharmacokinetic profiles and posttransplant complications are similar for once-daily iBU and traditional 4-times-daily iBU.
60例患者被随机分组，在造血细胞移植预处理治疗中接受静脉注射白消安（iBU），其中一组为0.8mg/kg，每天4次，持续2小时（BU4组），另一组为3.2mg/kg，每天1次，持续3小时（BU1组）。从所有患者中获取了首次白消安剂量的完整药代动力学参数，两组之间具有可比性：BU4组和BU1组的消除半衰期（均值±标准差）分别为2.75±0.22小时和2.83±0.21小时，估计每日曲线下面积（AUC）分别为6058.0±1091.9和6475.5±1099.4微摩尔·分钟/天，清除率分别为2.05±0.36和1.91±0.31毫升/分钟/千克。两组移植后的植入时间相似。急性移植物抗宿主病（aGVHD）和肝静脉闭塞病（VOD）的发生率无明显差异。此外，移植后100天内观察到的其他毒性在两组之间也无显著差异。BU4组的非复发死亡率累积发生率为20.8%，BU1组为13.3%。总之，我们的随机研究表明，每日一次的iBU和传统的每日4次的iBU的药代动力学特征和移植后并发症相似。
