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

Miki Sato, Shinichi Kako, Kana Matsumoto, 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 TanakaJunya Kanda, Junji Nishida, Kunihiko Morita, Yoshinobu Kanda

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)497-504
Number of pages8
JournalInternational journal of hematology
Volume101
Issue number5
DOIs
Publication statusPublished - 2015 May 1
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Hematology

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  • Cite this

    Sato, M., Kako, S., Matsumoto, K., Oshima, K., Akahoshi, Y., Nakano, H., Ugai, T., Yamasaki, R., Wada, H., Ishihara, Y., Sakamoto, K., Kawamura, K., Ashizawa, M., Terasako-Saito, K., Kimura, S. I., Nakasone, H., Kikuchi, M., Tanihara, A., Yamazaki, R., ... Kanda, Y. (2015). Pharmacokinetics study of once-daily intravenous busulfan in conditioning regimens for hematopoietic stem cell transplantation. International journal of hematology, 101(5), 497-504. https://doi.org/10.1007/s12185-015-1756-6