Bioequivalence studies on bisphosphonates: the example of alendronate.

The study was designed to evaluate the bioequivalence of two formulations of alendronate (CAS 121268-17-5, Osalen 10 mg tablets, in the following referred to as "test" vs. the originator product, in the following referred to as "reference") in 89 healthy male and female volunteers, who were administered four 10 mg alendronate tablets under fasting conditions. The trial was performed according to an open, randomized, cross-over design with a wash-out period of 14 days in one study center. Urine samples were taken up to 36 h post dose, and the concentrations of alendronate were determined by HPLC/Fl method. The mean Ae0-36 were 102.89 +/- 57.52 microg and 96.23 +/- 60.81 microg for the test and reference formulations, respectively, while the mean Rmax were 36.15 +/- 21.07 microg/h and 35.36 +/- 22.88 microg/h, respectively. The test and reference tablets Tmax were 0.592 +/- 0.858 h and 0.583 +/- 0.858 h, respectively. No significant differences of pharmacokinetic parameters between the two studied formulations were found. The 90% confidence interval for the primary target parameters, intra-individual ratios of Ae0-36 and Rmax of alendronate were between 1.01 and 1.17 for Ae0-36 and between 0.96 and 1.11 for Rmax, and thus within the acceptance range for bioequivalence trials. In the light of the present study it can be concluded that alendronate test tablets are bioequivalent to the reference formulation.