Pharmacokinetic and Bioequivalence Studies of 2 Metformin Glibenclamide Tablets in Healthy Chinese Subjects Under Fasting and Fed Conditions

Abstract

AbstractThe rational combination of oral antidiabetic agents is more likely to provide better glycemic control than monotherapy. Metformin glibenclamide tablets can be used as second‐line therapy for patients with type 2 diabetes mellitus who cannot successfully control their blood glucose levels by diet and exercise plus metformin or sulfonylureas. The aim of this study was to evaluate the bioequivalence and safety of metformin hydrochloride and glibenclamide tablets (500 mg/5 mg) prepared by 2 different vendors in healthy Chinese subjects under fasting and fed conditions. This is an open‐label, single‐center, randomized, 2‐formulation, 2‐period crossover study. After screening, 40 subjects were enrolled in the fasting trial, while 40 subjects were enrolled in the fed trial. Qualified subjects were randomly assigned to receive a monotherapy dose of 500 mg/5 mg of the test or reference formulation, and after a 1‐week washout period, they took the alternative formulation. Blood samples were collected from 24 blood collection sites per cycle for pharmacokinetic analysis until 36 hours after oral administration. In total, 78 subjects completed the study. Under fasting and fed conditions, the geometric mean ratios of maximum plasma concentration, area under the plasma concentration–time curve (AUC) from time 0 to time of last quantifiable drug level , and AUC from time 0 to infinity between the 2 products, as well as the corresponding 90%CIs, were all within the range of 80%–125%. It was found that exposure (AUC from time 0 to infinity) to metformin is decreased by about 25% in the fed state compared to fasting, whereas glibenclamide exposure is increased by about 30% in the fed state. No severe adverse events were observed in the study.