Pharmacokinetics and Bioequivalence of Sitagliptin Phosphate/Metformin Hydrochloride Tablets in Healthy Chinese Subjects: A Randomized, Open, Crossover Study

Abstract

\n Objective To evaluate the pharmacokinetics and bioequivalence between Sitagliptin Phosphate/metformin Hydrochloride Tablets (test formulation) at a single dose of 50mg/850mg and Sitagliptin Phosphate/metformin Hydrochloride Tablets (reference formulation, JANUMET®) at a single dose of 50mg/850mg in healthy Chinese subjects.Methods The study was designed as a randomized, open-lable, two-period double-crossover trial. A total of 24 volunteers under fasting condition and 24 subjects under fed condition were given a single oral dose of 50mg/850mg Sitagliptin Phosphate/metformin Hydrochloride Tablets of test and reference, respectively. Liquid chromatography Tandem mass spectrometry (LC-MS/MS) method was used to determine the concentrations of sitagliptin and metformin in the plasma of subjects. The pharmacokinetic parameters were calculated by WinNonlin 7.0 program and the bioequivalence was evaluated by SAS 9. 4program. Results The 90% confidential interval (CI) of geometric mean ratio under fasting condition for Cmax, AUC0-t and AUC0-∞ of sitagliptin between the test group and the reference group were 101.70%-120.62%, 99.81%-105.61%, 100.27%-106.12% and metformin were 90.39%-111.48%, 94.76%-109.12%, 95.76%-110.38%. The 90% CI of geometric mean ratio under fed condition for Cmax, AUC0-t and AUC0-∞ between the test group and the reference group were 102.12%-117.31%, 100.80%-107.81%, 100.82%-107.78% and metformin were 95.53%-105.22%, 92.76%-103.07%, 93.40%-104.14%. Both were generally well tolerated.Conclusion The two formulations of Sitagliptin Phosphate/metformin Hydrochloride Tablets were bioequivalent under fasting and fed condition in healthy Chinese subjects.Trial registration Clinical Trial Registry (trial ID: NCT04877106).