ABSTRACT
BACKGROUND: Miglitol is an α-glucosidase inhibitor (AGI) used as an antihyperglycemic agent in the treatment of type 2 diabetes mellitus. The mechanism is that miglitol binds to and inhibits the α-glucosidase reversibly in the proximal intestine. Thus, carbohydrates not digested in the upper small intestine are transported to the lower intestine where they are eventually digested. OBJECTIVE: This study was performed for the subsequent marketing of the test miglitol formulation in Korea. We evaluated the comparative bioavailability and tolerability of the test and reference formulations in healthy male adult volunteers. METHODS: A total of 40 healthy adult subjects were enrolled in this single-dose, randomized, open-label, 2-period, 2-sequence, crossover bioequivalence study. During each period, subjects received 100 mg of miglitol test or reference. Blood samples from the subjects were obtained before dosing at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 9, and 12 hours after oral drug administration. Plasma concentrations were determined by using liquid chromatography/mass spectrometry/mass spectrometry (LC-MS/MS). The PK parameters including AUCt, AUC∞, Cmax, and tmax were measured and all treatment-emergent adverse events (TEAEs) and their relationships to study these medications were recorded throughout the entire study. RESULTS: A total of 40 healthy adult male Korean subjects were enrolled in the study and randomized into two treatment groups. Ultimately, 33 subjects completed the study. During each treatment period, blood samples were collected at specific time intervals from 0 to 12 hours after administration of a single drug dose. The PK parameters including AUCt, AUC∞, Cmax, and tmax were calculated and the 90% CIs of the ratio (test/reference) of the parameters were obtained by analysis of variance (ANOVA) on logarithmically transformed data. The 90% CIs of the geometric mean ratios for the test to reference formulations were as follows: 1.05 (0.97 - 1.13) for AUCt and 1.05 (0.96 - 1.14) for Cmax. Statistical analysis confirmed that the 90% CIs for these PK parameters were within the commonly accepted bioequivalence range of 0.8 - 1.25. There were no serious or unexpected TEAEs during the study. CONCLUSIONS: In the healthy adult Korean subjects, the test and reference formulations had similar PK parameters and similar plasma concentration-time profiles. The test formulation of miglitol met the Korean regulatory criteria (AUCt and Cmax) for assuming bioequivalence and both formulations were generally well-tolerated. The CRiS identifiers: KCT0000770.
