Pharmacokinetics study of once-daily intravenous busulfan in conditioning regimens for hematopoietic stem cell transplantation

作者：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^*

来源：International Journal of Hematology, 2015, 101(5): 497-504.

DOI：10.1007/s12185-015-1756-6

• Once-daily intravenous busulfan
• Hematopoietic stem cell transplantation
• Conditioning regimen
• Pharmacokinetics
• Area under the plasma concentration versus time curve

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 mu mol x min/L (range 3491-6284 mu mol x 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.

• 出版日期2015-5