Bioequivalence Evaluation of Two Metformin/Empagliflozin Fixed-Dose Combination Tablets in Healthy Chinese Subjects
Yuyan Lei1,2, Qin Yi3, Shan Ji2
1Office of the Drug Clinical Trial Institution, The Second Nanning People's Hospital, Nanning, Guangxi, China.
Abstract:
This study evaluated the bioequivalence and safety of two fixed-dose combination (FDC) tablet formulations of metformin/empagliflozin (1000 mg/5 mg) in healthy Chinese subjects. A single-center, open-label, randomized, two-period, two-treatment, and two-sequence crossover study was conducted, enrolling 56 subjects who were assigned to either fasting or fed conditions in a 1:1 ratio. Each subject received both the test and reference formulations, with a 7-day washout period between administrations. Blood samples were collected up to 48 h post-dose, and plasma concentrations of metformin and empagliflozin were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Bioequivalence was assessed based on key pharmacokinetic parameters-Cmax, AUC0-t, and AUC0-∞-with the geometric least-squares mean ratios of the test to reference formulation falling within the accepted bioequivalence range of 80.00% to 125.00% for all 90% confidence intervals under both fasting and fed states. High-fat meals significantly reduced the Cmax of metformin and empagliflozin by approximately 47% and 28%, respectively, and their overall exposure (AUC0-∞) by approximately 29% and 15%, respectively. No serious adverse events were reported. In conclusion, the test and reference formulations of metformin/empagliflozin FDC tablets were bioequivalent and well-tolerated under both fasting and fed conditions.
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