Dose-Proportional Pharmacokinetics of Risedronate on Single-Dose Oral Administration to Healthy Volunteers

Risedronate is a pyridinyl bisphosphonate approved for the treatment of Paget's disease (US‐FDA) and in development for the treatment and prevention of osteoporosis. This study examined risedronate pharmacokinetics and tolerability after oral administration using a randomized, double‐blind, par...

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Bibliographic Details
Published in:	Journal of clinical pharmacology Vol. 40; no. 3; pp. 258 - 265
Main Authors:	Mitchell, David Y., Eusebio, Rachelle A., Sacco-Gibson, Nancy A., Pallone, Karen A., Kelly, Sandra C., Nesbitt, John D., Brezovic, Christopher P, Thompson, Gary A., Powefl, James H.
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-03-2000 SAGE Publications Sage Science
Subjects:	Administration, Oral Adult Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Dose-Response Relationship, Drug Etidronic Acid - administration & dosage Etidronic Acid - adverse effects Etidronic Acid - analogs & derivatives Etidronic Acid - pharmacokinetics Female Humans Male Medical sciences Pharmacology. Drug treatments Risedronic Acid Human Healthy subject Risedronic acid Toxicity Single dose Oral administration Diphosphonic acid derivatives Pharmacokinetics Bisphosphonates Dose activity relation
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Summary:	Risedronate is a pyridinyl bisphosphonate approved for the treatment of Paget's disease (US‐FDA) and in development for the treatment and prevention of osteoporosis. This study examined risedronate pharmacokinetics and tolerability after oral administration using a randomized, double‐blind, parallel‐group design. Healthy male and female volunteers (n = 22–23 subjects per dose) received a single oral dose of 2.5, 5, or 30 mg risedronate. Serum and urine samples were collected for 72 and 672 hours, respectively, and risedronate concentrations were determined by ELISA. Safety was evaluated by monitoring adverse events, clinical laboratory measurements, vital signs, and electrocardiograms. Mean Cmax (0.41, 0.94, and 5.1 ng/mL for 2.5, 5, and 30 mg, respectively), AUC (1.8, 3.9, and 21 ng•h/mL for 2.5, 5, and 30 mg, respectively), and urinary excretion (22, 63, and 260 μg for 2.5, 5, and 30 mg, respectively) were dose proportional, and there were no significant differences in tmax or CLR among the three doses. All doses were well tolerated; no serious adverse events occurred, and all but one of the adverse events were mild or moderate in severity. There was no evidence of an acute phase reaction occurring after oral administration of risedronate.
Bibliography:	ark:/67375/WNG-NNVDZVT8-0 ArticleID:JCPH743 istex:D0DAB8073CE1D8A0A327AA83E6658F552854E65F
ISSN:	0091-2700 1552-4604
DOI:	10.1177/00912700022008928