title: Blood distribution of bortezomib and its kinetics in multiple myeloma patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Osawa
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Naito
authors.affiliation: 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.
authors.forename: Takanori
authors.initials: T
authors.lastname: Kaneko
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Mino
authors.affiliation: Oncology Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ohnishi
authors.affiliation: Department of Drug Evaluation & Informatics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka, Shizuoka 422-8526, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamada
authors.affiliation: 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.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kawakami
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001897:Boronic Acids / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage; D004906:Erythrocyte Count; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood*; D010949:Plasma / Q000737:chemistry; D011719:Pyrazines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone
keywords: Blood distribution; Bortezomib; Multiple myeloma; Pharmacokinetics; Therapeutic drug monitoring