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 gemigliptin), 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. There 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.

Author Details

Authors

• Sang Won Lee¹
• Sang-In Park¹
• SeungHwan Lee¹
• Jae-Yong Chung²
• Kyung-Sang Yu¹

Departments

• ¹ Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul,
• ² Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam, Korea

Address

Kyung-Sang Yu, MD, PhD

Department of Clinical Pharmacology and Therapeutics
Seoul National University College of Medicine and Hospital
101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea

Email: [email protected]

Citation