Pharmacokinetics of two formulations of alendronate sodium/cholecalciferol (vitamin D3) tablets 70 mg/5600 IU: An open-label, randomized, single-dose, two-treatment, two-period, two-sequence, cross-over, bioequivalence study

Abstract

Abstract A fixed dose combination of alendronate and cholecalciferol (vitamin D3) 70 mg/5600 IU tablets has been indicated for the treatment of osteoporosis. This study was aimed to assess bioequivalence between test and reference formulations of alendronate sodium/cholecalciferol (vitamin D3) tablets 70 mg/5600 IU in 110 healthy adult male volunteers under fasting conditions. This was an open label, randomized, single dose, two way cross-over study, separated by a washout period of 14 days. All possible efforts were made to stabilize the baseline endogenous levels of cholecalciferol. Blood samples were collected from 96 h pre-dose to 96 h post-dose and 0–24 h for cholecalciferol and alendronate, respectively. Quantification of alendronate and cholecalciferol was done using distinct validated LC-MS/MS methods. Two baseline adjusted methods, method-I (subtraction of the average concentration from each post-dose concentration) and method-II (subtraction of the individual AUC from post-dose AUC) were applied for deriving the AUC0–t parameter of cholecalciferol, among which bioequivalence was concluded based on data obtained using method-I. The 90% CI of Cmax and AUC0–t for alendronate and baseline adjusted cholecalciferol were within the regulatory acceptance limit of 80.00–125.00% and considered as bioequivalent.