CLINICAL-PHARMACOLOGY OF ALENDRONATE SODIUM

Clinical studies have been performed to investigate the pharmacokineti cs and pharmacodynamics of alendronate, an inhibitor of bone resorptio n for the treatment of osteoporosis. Alendronate is one of the most po tent bisphosphonates currently undergoing clinical investigation (> 10 0-fold more potent than etidronate in vivo). The pharmacokinetics of a lendronate are similar to those of other bisphosphonates. After a 2-h intravenous infusion, plasma concentrations of alendronate decline rap idly to approximately 5% of initial values within 6 h. About 50% of a systemic dose is excreted unchanged in the urine in the 72 h following administration. By analogy to its behavior in animals the remainder i s assumed to be taken up by the skeleton. After sequestration into bon e, the elimination of alendronate is very prolonged. The terminal half -life was estimated to be greater than 10 years. Despite prolonged ske letal residence, the biological effects of alendronate begin to dimini sh post-treatment, since the duration of effect reflects factors besid es dose and cumulative drug exposure. When taken after an overnight fa st, 2 h before breakfast, the oral bioavailability of alendronate aver ages approximately 0.75% of dose with substantial variability (coeffic ient of variation 55%-75%) both between and within subjects. Reducing the wait before food from 2 h to 1 h, or even 30 min, produces a mean reduction in absorption of 40%. Since the clinical efficacy of alendro nate is indistinguishable whether it is given 30 min, 1 h, or 3 h befo re a meal, the observed variability in bioavailability within this ran ge is of little consequence. Dosing up to at least 2 h after a meal dr amatically reduces absorption (80%-90%).