Sato Miki, Kako Shinichi, Matsumoto Kana, Oshima Kumi, Akahoshi Yu, Nakano Hirofumi, Ugai Tomotaka, Yamasaki Ryoko, Wada Hidenori, Ishihara Yuko, Sakamoto Kana, Kawamura Koji, Ashizawa Masahiro, Terasako-Saito Kiriko, Kimura Shun-Ichi, Nakasone Hideki, Kikuchi Misato, Tanihara Aki, Yamazaki Rie, Tanaka Yukie, Kanda Junya, Nishida Junji, Morita Kunihiko, Kanda Yoshinobu
Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma, Omiya-ku, Saitama, Saitama, 330-8503, Japan.
Int J Hematol. 2015 May;101(5):497-504. doi: 10.1007/s12185-015-1756-6. Epub 2015 Feb 12.
In Japan, intravenous busulfan (ivBu) is usually given four times per day as an infusion at 0.8 mg/kg over 2 h. However, as this requires a midnight administration, a once-daily infusion of ivBu at 3.2 mg/kg over 3 h has been investigated as a more convenient and safer method. In this study, 20 Japanese patients received once-daily ivBu in conditioning regimens before allogeneic hematopoietic stem cell transplantation (HSCT), and blood samples were obtained just before, and 3, 3.5, 5, 7, 10, and 24 h after the initiation of ivBu infusion. The outcomes of HSCT were evaluated prospectively. The median area under the plasma concentration versus time curve (AUC) of Bu was 5272 μmol × min/L (range 3491-6284 μmol × min/L), and was similar to those in previous once-daily ivBu studies and to the estimated daily AUC in previous 4-times-daily ivBu studies. All of the patients but two, who died early due to infection, achieved neutrophil engraftment at a median of 25 days after transplantation. No patient was diagnosed with veno-occlusive disease according to the criteria established by Jones. No regimen-related toxicity was significantly associated with AUC. In conclusion, once-daily administration of ivBu has a stable pharmacokinetic profile, and was safely performed in Japanese patients.
在日本，静脉注射白消安（ivBu）通常每天给药4次，以0.8mg/kg的剂量在2小时内输注。然而，由于这需要在午夜给药，因此研究了一种更方便、更安全的方法，即每天一次以3.2mg/kg的剂量在3小时内输注ivBu。在本研究中，20例日本患者在异基因造血干细胞移植（HSCT）前的预处理方案中接受了每日一次的ivBu治疗，并在ivBu输注开始前、开始后3、3.5、5、7、10和24小时采集血样。对HSCT的结果进行了前瞻性评估。白消安的血浆浓度-时间曲线下面积（AUC）中位数为5272μmol×min/L（范围为3491-6284μmol×min/L），与既往每日一次ivBu研究中的结果以及既往每日4次ivBu研究中的估计每日AUC相似。除两名因感染早期死亡的患者外，所有患者均在移植后中位数25天实现了中性粒细胞植入。根据琼斯制定的标准，没有患者被诊断为静脉闭塞性疾病。没有任何方案相关毒性与AUC显著相关。总之，每日一次给药的ivBu具有稳定的药代动力学特征，并且在日本患者中安全实施。
