Takashi Osawa1, Takafumi Naito1, Takanori Kaneko2, Yasuaki Mino1, Kazunori Ohnishi3, Hiroshi Yamada4, Junichi Kawakami5. 1. Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan. 2. 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. 3. Oncology Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan. 4. Department of Drug Evaluation & Informatics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka, Shizuoka 422-8526, Japan. 5. Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan. Electronic address: kawakami-ham@umin.ac.jp.
Abstract
OBJECTIVES: 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. DESIGN AND METHOD: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVES: 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 myelomapatients. DESIGN AND METHOD: Eighteen multiple myelomapatients 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. RESULTS: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. CONCLUSION: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 myelomapatients.
Authors: Julie M Janssen; T P C Dorlo; D Niewerth; A J Wilhelm; C M Zwaan; J H Beijnen; A Attarbaschi; A Baruchel; F Fagioli; T Klingebiel; B De Moerloose; G Palumbo; A von Stackelberg; G J L Kaspers; A D R Huitema Journal: Clin Pharmacokinet Date: 2020-02 Impact factor: 6.447
Authors: Seth M Schneider; Suzanne M Pritchard; George A Wudiri; Chasity E Trammell; Anthony V Nicola Journal: mBio Date: 2019-05-14 Impact factor: 7.867