Pharmacokinetics of intravenous busulfan as condition for hematopoietic stem cell transplantation: comparison between combinations with cyclophosphamide and fludarabine.

International journal of hematology 2021 Jan

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Busulfan (Bu) has been used in combination with fludarabine (Flu; BuFlu) or cyclophosphamide (Cy; BuCy) as conditioning for allogeneic hematopoietic stem cell transplantation (HSCT). This multi-institutional prospective study compared pharmacokinetic (PK) parameters of Bu between BuFlu and BuCy. Plasma Bu concentrations were measured by high-performance liquid chromatography at the first dose of the first and fourth days of intravenous Bu administrations (total of 16 doses of 0.8 mg/kg). Thirty-seven patients were evaluable (BuFlu, N = 18; BuCy, N = 19). The median age was significantly higher in BuFlu. In BuFlu, the median area under the blood concentration-time curve of Bu on the fourth day was 1183 μmol min/L (range 808-1509), which was significantly higher than that on the first day [1095 μmol min/L (range 822-1453), P < 0.01]. In contrast, such differences were not observed in BuCy. Consistently, there was a significant decrease in the clearance of Bu on the fourth day as compared with the first day in BuFlu. These results suggest that the PK of Bu was altered during the co-administration of Flu, which was not the case with Cy. A large-scale study is required to evaluate the significance of the differences in the PK of Bu between the conditionings on HSCT outcomes.

Citation

Taku Kikuchi, Takehiko Mori, Chikako Ohwada, Masahiro Onoda, Hiroaki Shimizu, Hiroki Yokoyama, Makoto Onizuka, Yuya Koda, Jun Kato, Yusuke Takeda, Yutaro Hino, Tatsuzo Mishina, Emiko Sakaida, Katsuhiro Shono, Yuhei Nagao, Akira Yokota, Kana Matsumoto, Kunihiko Morita, Shinichiro Okamoto, Kanto Study Group for Cell Therapy (KSGCT). Pharmacokinetics of intravenous busulfan as condition for hematopoietic stem cell transplantation: comparison between combinations with cyclophosphamide and fludarabine. International journal of hematology. 2021 Jan;113(1):128-133