Blood distribution of bortezomib and its kinetics in multiple myeloma patients

• Published in: Clinical biochemistry Vol. 47; no. 15; pp. 54 - 59
• Main Authors: Osawa, Takashi, Naito, Takafumi, Kaneko, Takanori, Mino, Yasuaki, Ohnishi, Kazunori, Yamada, Hiroshi, Kawakami, Junichi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2014
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Blood distribution; Boronic Acids - administration & dosage; Boronic Acids - blood; Boronic Acids - pharmacokinetics; Bortezomib; Dexamethasone - administration & dosage; Erythrocyte Count; Female; Humans; Male; Middle Aged; Multiple myeloma; Multiple Myeloma - blood; Pharmacokinetics; Plasma - chemistry; Pyrazines - administration & dosage; Pyrazines - blood; Pyrazines - pharmacokinetics; Therapeutic drug monitoring; Therapeutic drug monitoring; LC-MS/MS; RSD; Bortezomib; Multiple myeloma; CYP; IQR; Pharmacokinetics; Blood distribution
• ISSN: 0009-9120; 1873-2933
• DOI: 10.1016/j.clinbiochem.2014.06.077

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. [Display omitted] •Bortezomib concentration in whole blood rose within the cycle.•Bortezomib concentration in whole blood was comparable between the cycles.•Bortezomib concentration in whole blood was 7-fold higher than that in plasma.•The blood bortezomib concentration was correlated with the red blood cell count.•The half-life of bortezomib in whole blood was 23days.