Pharmacokinetic comparison of gemigliptin 50 mg and metformin 500 mg as a fixed-dose combination and loose combination

Abstract

Background: Metformin and dipeptidyl peptidase-4 (DPP-IV) inhibitors are commonly combined to treat patients with diabetes mellitus (DM). A new fixed-dose combination (FDC) drug containing gemigliptin, a DPP-IV inhibitor, and sustained-release metformin has been developed. This study aimed to compare the PKs and tolerability of FDC versus loose combination of gemigliptin 50 mg and metformin 500 mg. Materials and methods: A randomized, open-label, two-treatment two-period, two-sequence, crossover study was conducted in 28 healthy subjects, who received a single oral dose of an FDC tablet of gemigliptin (50 mg) and sustained-release metformin (500 mg) or were coadministered gemigliptin (50 mg) and extended-release metformin (500 mg) with a 1-week washout. Serial blood samples were collected up to 48 hours after study drug administration, and the plasma concentrations of gemigliptin. LC15-0636 (active metabolite of gcmigliptin), and metformin were determined using a validated LC-MS/MS method. Pharmacokinetic parameters were derived using a noncompartmental method. Safety and tolerability were evaluated based on vital signs, adverse events, clinical laboratory tests, and electrocardiography. Results: The concentration-time profiles of gemigliptin and metformin were similar when they were administered as FDC or were coadministered. The geometric mean ratio (GMR) and its 90% CIs of C-max for gemigliptin, LC15-0636, and metformin were 0.93 (0.85 - 1.02), 1.00 (0.94 - 1.06). and 1.03 (0.98 - 1.09). respectively. The corresponding values of AUC(last) were 0.97 (0.93 - 1.01), 1.00 (0.97 - 1.04), and 1.00 (0.95 - 1.05), respectively. Them were no clinically meaningful differences in safety and tolerability. Conclusion: When comparing the AUC(last )and C-max of gemigliptin, LC15-0636, and metformin, the 90% CIs were all within the range of 0.8 -1.25, which is the commonly accepted range for evaluating bioequivalence.