Dose-proportional pharmacokinetics of risedronate on single-dose oral administration to healthy volunteers

Risedronate is a pyridinyl bisphosphonate approved for the treatment of Pag et's disease (US-FDA) and in development for the treatment and prevention o f osteoporosis. This study examined risedronate pharmacokinetics and tolera bility after oral administration using a randomized, double-blind parallel- group design. Healthy male and female volunteers (n = 22-23 subjects per do se) received a single oral dose of 2.5, 5 or 30 mg risedronate. Serum and u rine samples were collected for 72 and 672 hours, respectively, and risedro nate concentrations were determined by ELISA. Safety was evaluated by monit oring adverse events, clinical laboratory measurements, vital signs, and el ectrocardiograms. Mean C-max (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, resp ectively), and urinary excretion (22, 63, and 260 mu g for 2.5, 5 and 30 mg , respectively) were dose proportional, end there were no significant diffe rences in t(max) or CLR among the three doses. All doses were well tolerate d; no serious adverse events occurred, and all but one of the adverse event s were mild or moderate in severity There was no evidence! of an acute phas e reaction occurring after oral administration of risedronate. (C) 2000 the American College of Clinical Pharmacology.