Two-way Crossover Bioequivalence Study of Alendronate Sodium Tablets in Healthy, Non-smoking Male Volunteers under Fasted Conditions

Abstract

This study was conducted in order to assess the bioequivalence of two different formulations containing 70 mg alendronate sodium (CAS 121268-17-5) under fasted conditions. One hundred twenty-two healthy male volunteers were enrolled in an open label, randomized, crossover design with a wash-out period of 20 days in one study center. Urine samples were collected up to 36 h post-dose, and the concentrations of alendronic acid were determined using a high performance liquid chromatographic method with pre-derivatization and fluorescence detection (HPLC/FL) method. The mean Ae0?t were 604.24 ? 348.73 ?g and 627.36 ? 327.99 ?g, while the mean Rmax were 193.87 ? 114.68 ?g/h and 202.00 ? 107.83 ?g/h for the test and reference formulations, respectively. The Tmax of the test and reference tablets were 1.26 ? 0.58 h and 1.26 ? 0.51 h, respectively. No significant differences of pharmacokinetic parameters between the two studied formulations were found. The 90% confidence intervals for the primary target parameters, intra-individual ratios for Ae0?t and Rmax of alendronic acid, were between 0.86?1.00 and 0.85?1.01, respectively, and thus within the acceptance range for bioequivalence criteria. In the light of the present study it can be concluded that the test formulation is bioequivalent to the reference formulation.

Bioequivalence of generic alendronate sodium tablets (70 mg) to Fosamax^® tablets (70 mg) in fasting, healthy volunteers: a randomized, open-label, three-way, reference-replicated crossover study

“…In a classical, typical bioequivalence study, 122 subjects were enrolled because of the high within-subject CV for urine parameters, 37.42% for A e 0– t , and 40.05% for R max 19. Rhim et al20 were the first to assess the bioequivalence of alendronate by determining its plasma concentrations in a two-period crossover study involving 23 Korean subjects; the results demonstrated bioequivalence even though the study power was <60%.…”