Osawa Takashi, Naito Takafumi, Kaneko Takanori, Mino Yasuaki, Ohnishi Kazunori, Yamada Hiroshi, Kawakami Junichi
Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan.
Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan; Department of Drug Evaluation & Informatics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka, Shizuoka 422-8526, Japan.
Clin Biochem. 2014 Oct;47(15):54-9. doi: 10.1016/j.clinbiochem.2014.06.077. Epub 2014 Jul 8.
Pharmacokinetic disposition of bortezomib in the blood has not been fully characterized in humans. This study aimed to evaluate the blood distribution of bortezomib and its kinetics in multiple myeloma patients.
Eighteen multiple myeloma patients receiving bortezomib-dexamethasone combination therapy were enrolled. Blood specimens were drawn just before bortezomib administration on days 1 and 8 in the second and third cycles and after discontinuation. The relationships between bortezomib concentration and blood components were evaluated.
Bortezomib concentration in the blood on day 1 was higher than that on day 8 in the second cycle. No difference was observed in bortezomib blood concentrations between day 8 in the second and third cycles. The bortezomib concentration in the blood and blood cells was 3- and 7-fold higher than that in plasma. Bortezomib concentration in the blood was correlated with the red blood cell count. The half-life of bortezomib in the blood was 23days.
Bortezomib was taken up into red blood cells to only a limited extent and eliminated in parallel to the red blood cells' lifespan. The turnover of red blood cells can affect the pharmacokinetic disposition of bortezomib in multiple myeloma patients.
硼替佐米在人体血液中的药代动力学分布尚未完全明确。本研究旨在评估硼替佐米在多发性骨髓瘤患者中的血液分布及其动力学。
纳入18例接受硼替佐米-地塞米松联合治疗的多发性骨髓瘤患者。在第二和第三周期的第1天和第8天硼替佐米给药前及停药后采集血样。评估硼替佐米浓度与血液成分之间的关系。
第二周期第1天血液中的硼替佐米浓度高于第8天。第二和第三周期第8天的硼替佐米血药浓度无差异。血液和血细胞中的硼替佐米浓度分别比血浆中的高3倍和7倍。血液中的硼替佐米浓度与红细胞计数相关。硼替佐米在血液中的半衰期为23天。
硼替佐米仅在有限程度上被红细胞摄取，并与红细胞寿命平行消除。红细胞更新可影响硼替佐米在多发性骨髓瘤患者中的药代动力学分布。
