Evaluation of Bioequivalency and Pharmacokinetic Parameters for Two Formulations of Glimepiride 1-mg in Chinese Subjects

PURPOSE: Glimepiride, an FDA-approved oral hypoglycemic drug, is a long-acting sulfonylurea (SU), used for treating type 2 diabetes. The study aimed to evaluate the bioequivalence and safety profiles of two different formulations of glimepiride 1 mg from two different manufactures in healthy Chinese subjects in the fasting and fed state in order to acquire adequate pharmacokinetic evidence for registration approval of the test formulation. PATIENTS AND METHODS: This study is an open-label, two-period, two-sequence, randomized, two-way crossover pharmacokinetic study in healthy Chinese subjects in the fasting and fed state. Seventy-two subjects were randomly assigned to the fasting group and the fed group (n=36 each). We collected blood samples, 24-h post drug administration. The plasma concentration of glimepiride was assessed using HPLC coupled with mass spectrometry. The following parameters were evaluated: AUC(0-inf), AUC(0-last), C(max), t(1⁄2), T(max), and λ(z). Safety was determined based on the occurrence of adverse events (AEs) and laboratory examinations (biochemistry, hematology, and urinalysis) throughout the entire study period. RESULTS: The geometric mean ratios (GMR) amongst the two glimepiride formulations for the primary pharmacokinetic parameters, ie, AUC(0-inf), AUC(0-last), and C(max) as well as the corresponding 90% CIs, were all within the range of 80.00–125.00% in the fasting and fed state. The safety profile for both treatments was comparable. CONCLUSION: PK analysis revealed that the test and reference formulations of glimepiride were bioequivalent and well tolerated in healthy Chinese subjects. Chinese Clinical Trials Registry identifier: CTR20171121. CLINICAL TRIAL REGISTRATION NUMBER: CTR20171121.