Pharmacokinetic Comparison and Bioequivalence Evaluation of Two Empagliflozin/Metformin Fixed-Dose Combination Tablets in Healthy Subjects under Fed Conditions
Background: Empagliflozin, an SGLT2 inhibitor, and Metformin, a biguanide, are commonly prescribed together for the management of type 2 diabetes. This study evaluates the bioequivalence of a fixed-dose combination of Empagliflozin and Metformin (12.5/1000 mg) in healthy subjects under fed conditions. The goal is to ensure that generic versions deliver the same therapeutic effect as the reference product. MaterialsandMethods: This study was a randomized, open-label, two-period, two-sequence, crossover trial aimed at evaluating the bioequivalence (BE) profiles of two fixed-dose combinations (FDCs) of Empagliflozin and Metformin. The assessment of bioequivalence focused on the maximum plasma concentration (Cmax), area under the concentration-time curve from time zero to time t (AUC0-t), and area under the concentration-time curve from time zero to infinity (AUC0-∞) for both the test and reference formulations. Out of 46 screened participants, 17 were enrolled, of whom 15 completed both treatment periods. In each period, serial blood samples were collected for a duration of up to 72 hours following the oral administration of the study medications. Plasma concentrations of Empagliflozin and Metformin were quantified using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology. The drug products were deemed bioequivalent if the 90% confidence interval (CI) for the test/reference ratios was within the range of 80.00% to 125.00% for the natural logarithm-transformed Cmax, AUC0-t, and AUC0-∞. Tolerability and safety were continuously monitored throughout the study. Results: Based on the rate and extent of absorption, the pharmacokinetic (PK) parameters were similar between the test product (T) and reference product (R). The 90% CI of the test/reference ratios of log-transformed PK parameters point estimates for Empagliflozin were Cmax: 97.39% (87.80% - 108.02%), AUC0-t: 95.40% (90.67% - 100.37%), and AUC0-∞: 95.98% (90.93% - 101.32%) and Cmax: 96.72% (84.39% - 110.84%), AUC0-t: 98.30% (89.94% - 107.43%), and AUC0-∞: 97.69% (89.53% - 106.59%) for Metformin, respectively (90% CI for all PK parameters fell within 80.00% - 125.00%). Conclusion: Our findings confirmed in vivo bioequivalence between the test and reference formulations of Empagliflozin 12.5 mg/Metformin 1000 mg under fed conditions.
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