title: The optimal oral dose selection of ibandronate in Japanese patients with osteoporosis based on pharmacokinetic and pharmacodynamic properties.
abstract: Ibandronate is a drug widely used outside Japan for the treatment of osteoporosis. It is available in formulations for intermittent intravenous (i.v.) administration and for intermittent (once monthly) oral administration. Ibandronate was recently approved in Japan as an i.v. injection with a dosing regimen of 1.0 mg once a month. To establish the optimal dose for oral administration of ibandronate in Japanese osteoporotic patients, we investigated the pharmacokinetics of and pharmacodynamic response to ibandronate following oral and intravenous administrations to Japanese subjects. Ibandronate (20, 50, 100, or 150 mg) was given orally to healthy postmenopausal Japanese women and to Japanese patients with primary osteoporosis. Serial measurements were obtained for the concentrations of serum ibandronate and urinary cross-linked C-telopeptide of Type I collagen (uCTX). Pharmacokinetic parameters and the time profiles of creatinine-corrected uCTX were compared with those obtained from postmenopausal Japanese women with osteopenia after administration of 1.0 mg i.v. ibandronate. Following oral administration of ibandronate, the area under the serum ibandronate concentration-time curve (AUCinf) increased dose-proportionally for doses up to 100 mg; at 150 mg, AUCinf increased beyond the dose-proportionality seen with doses up to 100 mg. The AUCinf within the linear range following administration of 100 mg oral ibandronate was similar to that following 1.0 mg i.v. ibandronate. Additionally, corrected uCTX decreased after administration of 100 mg oral ibandronate and remained decreased for 1 month; the magnitude of the decrease was similar to or greater than that obtained after 1.0 mg i.v. ibandronate. From a clinical pharmacological perspective, administration of 100 mg/month oral ibandronate was equivalent to that of 1.0 mg/month i.v. ibandronate.
authors.affiliation: Clinical Research Planning Department, Chugai Pharmaceutical Co., Ltd., 2-1-1, Nihonbashi Muromachi, Chuo-ku, Tokyo, 103-8324, Japan. nakaikyh@chugai-pharm.co.jp.
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Nakai
authors.affiliation: Clinical Research Planning Department, Chugai Pharmaceutical Co., Ltd., 2-1-1, Nihonbashi Muromachi, Chuo-ku, Tokyo, 103-8324, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tobinai
authors.affiliation: Primary Life Cycle Management Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Hashimoto
authors.affiliation: Clinical Research Planning Department, Chugai Pharmaceutical Co., Ltd., 2-1-1, Nihonbashi Muromachi, Chuo-ku, Tokyo, 103-8324, Japan.
authors.forename: Satofumi
authors.initials: S
authors.lastname: Iida
authors.affiliation: Clinical Research Planning Department, Chugai Pharmaceutical Co., Ltd., 2-1-1, Nihonbashi Muromachi, Chuo-ku, Tokyo, 103-8324, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Kawanishi
mesh_terms: D000284:Administration, Oral; D019540:Area Under Curve; D044466:Asian People; D024042:Collagen Type I / Q000378:metabolism; D004164:Diphosphonates / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077557:Ibandronic Acid; D007275:Injections, Intravenous / Q000379:methods; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism; D010455:Peptides / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D004164:Diphosphonates; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000077557:Ibandronic Acid
keywords: Ibandronate; Japanese; Pharmacodynamics; Pharmacokinetics