Bioequivalence of Alendronate and Vitamin D3 in a Combination Tablet in Healthy Taiwanese Volunteers, using a Novel Plasma Alendronate Assay

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 subjects. Methods In this open-label, randomized, two-period, crossover study, 68 volunteers were randomized to a single ALN/D5600 combination tablet or corresponding doses of ALN 70 mg + vitamin D3 5600 IU (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 (GMRs) of ALN area under the plasma concentration-time curve (AUC)0-last, AUC0-∞, and maximum observed concentration (Cmax), and unadjusted vitamin D3 AUC0-80h and Cmax, were compared and considered bioequivalent if the 90% confidence interval (CI) was within (0.8, 1.25). Findings The GMRs (90% CI) were: AUC0-last, 1.084 (0.937, 1.253); AUC0-∞, 1.081 (0.935, 1.249); Cmax, 1.112 (0.959, 1.289) for ALN, and AUC0-80h, 0.953 (0.827, 1.098); Cmax, 0.982 (0.854, 1.130) for vitamin D3 unadjusted for endogenous levels. Implications The combination tablet was considered bioequivalent to co-administration based on ALN AUC0-∞ and unadjusted vitamin D3 parameters. Slight differences for ALN AUC0-last and Cmax (upper 90% CIs outside the bounds) were not considered clinically significant. The combination tablet was well tolerated. No serious adverse experiences were reported.
Source: Current Therapeutic Research - Category: Drugs & Pharmacology Source Type: research