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

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Abstract
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.