Bioequivalence of Alendronate and Vitamin D₃ in a Combination Tablet Versus Corresponding-Dose Individual Tablets in Healthy Taiwanese Volunteers, Determined Using a Novel Plasma Alendronate Assay

Objective: This study was designed to demonstrate that alendronate (ALN)/vitamin D₃ combination tablets (ALN/D5600) are bioequivalent to corresponding doses of ALN and vitamin D₃ as individual tablets in healthy Taiwanese volunteers. Methods: In this open-label, randomized, 2-period, crossover study, 68 volunteers were randomized to a single ALN/D5600 combination tablet or corresponding doses of 70 mg ALN + 5600 IU vitamin D₃ (2 × 2800 IU), followed by a 12-day washout period and administration of the alternate formulation. Plasma ALN levels were measured using a newly developed assay. Geometric mean ratios of ALN AUC_0-last, AUC_0-∞, and C_max, and unadjusted vitamin D₃ AUC_0-80h and C_max were compared and considered bioequivalent if the 90% CI was within 0.8 to 1.25. Results: The geometric mean ratios were: AUC_0-last, 1.084 (90% CI, 0.937-1.253); AUC_0-∞, 1.081 (90% CI, 0.935-1.249); and C_max, 1.112 (90% CI, 0.959-1.289) for ALN, and AUC_0-80h 0.953 (90% CI, 0.827-1.098) and C_max, 0.982 (90% CI, 0.854-1.130) for vitamin D₃ unadjusted for endogenous levels. Conclusions: The combination tablet was considered bioequivalent to coadministration based on ALN AUC_0-∞ and unadjusted vitamin D₃ parameters. Slight differences for ALN AUC_0-last and C_max (upper 90% CIs outside the bounds) were not considered clinically significant. The combination tablet was well tolerated. No serious adverse experiences were reported.