Truncated Area under the Urinary Excretion Rate Curve in the Evaluation of Alendronate Bioequivalence after a Single Dose in Healthy Volunteers

Abstract

This study was designed to evaluate the bioequivalence of two formulations of alendronate (CAS 121268-17-5) 70 mg (test formulation, alendronate 70 mg tablets, vs. the reference formulation) in 80 healthy volunteers under fasting conditions. The trial followed an open, randomized, crossover design with a washout period of 28 days. Urine samples were collected up to 48 h post-dose, and the concentrations of alendronate were determined by HPLC. The mean Ae_0–48 was (mean ± SD) 152.15 ± 136.09 μg for the reference formulation and 150.37 ± 126.20 μg for the test formulation, while the mean R_max was 53.33 ± 41.53 μg/h and 55.85 ± 49.57 μg/h, respectively. No significant differences in pharmacokinetic parameters between the two formulations were found. The 90% confidence interval for the ratios of Ae_0–48 and R_max of alendronate were within the acceptance range for bioequivalence trials. The results of the present study suggest that the test formulation is bioequivalent to the reference formulation. The analyses of truncated AURC to shorter times showed similar values, which were within the range of bioequivalence.

Key words

Alendronate, bioequivalence, healthy volunteers, urinary bioequivalence - Anti-osteoporosis drug - CAS 121268-17-5 - Nitrogen-containing bisphosphonate

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