Pharmacokinetic bioequivalence of sitagliptin phosphate tablet formulations: a randomized, open-label, crossover study in healthy volunteers

Study Objectives: The aim of the current study is to assess the rate and extent of absorption of a test and reference formulation containing sitagliptin. Methods: An open-label, balanced, randomized, two-treatment, two-period, two-sequence crossover study was implemented to investigate the pharmacokinetic bioequivalence of a test and reference tablet products both containing a single dose of sitagliptin 100 mg in 28 healthy volunteers under fasting conditions. A total of twenty blood samples were obtained at pre-dose and multiple time intervals post-dose throughout the 48 hours sampling period. Sitagliptin concentrations were analysed using an LC-MS/MS validated method following a solid phase plasma extraction step. Sitagliptin pharmacokinetic parameters estimated with non-compartmental pharmacokinetic analysis were compared between the test and reference formulations with a multivariate analysis of variance. Results and Discussion: The differences between the reference and test formulations in terms of area under the curve, 0 to infinity ([AUC.sub.0-inf]), [AUC.sub.0-48], and the maximum concentration ([C.sub.max]) were found to be not significant. The 90% confidence intervals of sitagliptin Ln-transformed [AUC.sub.0-inf], [AUC.sub.0-48], and [C.sub.max], were within the pharmacokinetic bioequivalence acceptance range of 80%-125%. Conclusion: The test formulation of sitagliptin was bioequivalent in terms of exposure to the reference formulation in healthy volunteers under fasting conditions.