Bioequivalence of a fixed-dose repaglinide/metformin combination tablet and equivalent doses of repaglinide and metformin tablets .

Abstract

This study was conducted to determine whether a fixed-dose combination (FDC) tablet of repaglinide/metformin (2/500mg) is equivalent to coadministration of equivalent doses of individual (EDI) tablets of repaglinide (2mg) and metformin (500mg) in healthy Korean male subjects. This study was conducted as an open-label, randomized, single-dose, two-period, two-sequence crossover design in 50 healthy Korean male subjects who received an FDC tablet or EDI tablets. Plasma concentrations of repaglinide and metformin were determined for up to 24hours using a validated UPLC-MS/MS method. Bioequivalence was assessed according to current guidelines issued by the U.S. Food and Drug Administration (FDA) and Korean legislation. Tolerability was also evaluated throughout the study via subject interview, vital signs, and blood sampling. Point estimates (90% CIs) for AUC_0-t, AUC_0-∞, and C_max based on EDI tablets were 110.07 (102.25-118.49), 109.90 (101.70-118.39), and 112.60 (101.49-124.85), respectively, for repaglinide. They were 95.18 (89.62-101.05), 95.00 (89.74-100.65), and 98.44 (92.72-104.50), respectively, for metformin. These results satisfied the bioequivalence criteria of 80.00-125.00% proposed by the FDA and Korean legislation. Results of pharmacokinetic analysis suggested that repaglinide and metformin in FDC tablets were bioequivalent to EDI tablets of repaglinide (2mg) and metformin (500mg) in healthy Korean male subjects. Both formulations appeared to be well tolerated. .