title: Safety, pharmacokinetics, and changes in bone metabolism associated with zoledronic acid treatment in Japanese patients with primary osteoporosis.
abstract: Although once-yearly intravenous administration of zoledronic acid has been reported to inhibit bone resorption and increase bone mineral density, no studies have evaluated its effectiveness in treating osteoporosis in Japanese patients. Therefore, the purpose of this study was to investigate the pharmacokinetics and assess the safety of and changes in bone metabolism associated with zoledronic acid treatment in Japanese patients with primary osteoporosis. This was a single-administration study with a single-blind parallel-group design. The study participants were 24 Japanese patients with primary osteoporosis. The patients were divided into two groups, with each group receiving a single injection of zoledronic acid (4 or 5 mg). Pharmacokinetics and urinary excretion were then compared, and drug-related adverse events and changes in the levels of bone turnover markers were assessed at 12 months. Mean plasma concentrations of zoledronic acid peaked in both groups immediately after administration, and decreased to 1% or less of peak levels after 24 h. Noncompartmental analysis revealed that Cmaxand the area under the curve from time zero to infinity increased in proportion to the dose. The levels of bone resorption and formation markers decreased from day 15 and from 3 months after administration respectively, and suppression of these markers remained constant for the entire study period. No serious adverse events were reported. There was no large difference between the 4- and 5-mg groups in terms of pharmacokinetics, changes in the levels of bone turnover markers, and safety profiles. This study demonstrated acceptable pharmacokinetics and changes in bone metabolism associated with zoledronic acid treatment in female Japanese osteoporosis patients. Both the 4-mg dose and the 5-mg dose demonstrated acceptable safety and sustained antiresorptive effects for the duration of the study.
authors.affiliation: Department of Internal Medicine, Research Institute and Practice for Involutional Diseases, 1610-1 Meisei, Misato, Azumino, Nagano, 399-8101, Japan. ripid@bh.wakwak.com.
authors.forename: Masataka
authors.initials: M
authors.lastname: Shiraki
authors.affiliation: Asahi Kasei Pharma Corporation, 1-105 Kanda, Jinbocho, Chiyoda-ku, Tokyo, 101-8101, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Asahi Kasei Pharma Corporation, 1-105 Kanda, Jinbocho, Chiyoda-ku, Tokyo, 101-8101, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Asahi Kasei Pharma Corporation, 1-105 Kanda, Jinbocho, Chiyoda-ku, Tokyo, 101-8101, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Ueda
authors.affiliation: Aoba hospital, 2-15-2, Taishido, Setagaya-ku, Tokyo, 154-0004, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D000368:Aged; D044466:Asian People; D015415:Biomarkers / Q000097:blood; D001831:Body Temperature; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001862:Bone Resorption / Q000097:blood / Q000188:drug therapy; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D003710:Demography; D004164:Diphosphonates / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis; D010024:Osteoporosis / Q000097:blood / Q000188:drug therapy*; D016037:Single-Blind Method; D000077211:Zoledronic Acid
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: Bisphosphonates; Bone metabolism markers; Osteoporosis; Pharmacokinetics; Zoledronic acid