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

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Abstract

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.

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Conflict of interest

Y. Kanda received research funding and honorarium from the Otsuka Pharmaceutical Company.

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Authors and Affiliations

  1. Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma, Omiya-ku, Saitama, Saitama, 330-8503, Japan

    Miki Sato, Shinichi Kako, Kumi Oshima, Yu Akahoshi, Hirofumi Nakano, Tomotaka Ugai, Ryoko Yamasaki, Hidenori Wada, Yuko Ishihara, Kana Sakamoto, Koji Kawamura, Masahiro Ashizawa, Kiriko Terasako-Saito, Shun-ichi Kimura, Hideki Nakasone, Misato Kikuchi, Aki Tanihara, Rie Yamazaki, Yukie Tanaka, Junya Kanda, Junji Nishida & Yoshinobu Kanda

  2. Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts, Kyoto, Japan

    Kana Matsumoto & Kunihiko Morita

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  1. Miki Sato
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  2. Shinichi Kako
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  21. Junya Kanda
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Correspondence to Yoshinobu Kanda.

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Sato, M., Kako, S., Matsumoto, K. et al. Pharmacokinetics study of once-daily intravenous busulfan in conditioning regimens for hematopoietic stem cell transplantation. Int J Hematol 101, 497–504 (2015). https://doi.org/10.1007/s12185-015-1756-6

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  • DOI: https://doi.org/10.1007/s12185-015-1756-6

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