Pharmacokinetics and relative bioavailability of sitagliptin hydrochloride and sitagliptin phosphate tablets formulations: a randomized, open-label, crossover study in healthy male volunteers

Abstract

Introduction/Study Objectives: The present study aimed to evaluate the comparative bioavailability of a new generic sitagliptin formulation. Methods: This was an open label, randomized, balanced, two-sequence, two-treatment, two-period, single oral dose, crossover, bioequivalence (BE) study in 30 healthy male volunteers under fasting conditions. A 100 mg single dose of sitagliptin in the form of sitagliptin hydrochloride monohydrate (test) and sitagliptin phosphate monohydrate (reference) tablets were administered to each volunteer, separated by one week washout period. Twenty-two blood samples were collected at pre-dose and up until 48 hours post-dose. Sitagliptin concentrations were determined via a validated LC-MS/MS method following a protein precipitation step. Pharmacokinetic (PK) parameters were estimated via non-compartmental analysis and then compared between the reference and test formulations by performing a multivariate analysis of variance. Results and Discussion: No statistically significant difference was found between the test and reference formulations in terms of the maximum concentration (Cmax), area under the curve (AUC), AUC0-inf, and AUC0-48. The 90% confidence intervals of sitagliptin Ln-transformed Cmax, AUC0-inf, and AUC0-48 were within the regulatory BE acceptance range of 80%–125%. Conclusion: The test formulation met regulatory definition of BE to the reference formulation under fasting condition in these healthy male volunteers.