PMID- 37282359 OWN - NLM STAT- MEDLINE DCOM- 20230818 LR - 20230823 IS - 1752-8062 (Electronic) IS - 1752-8054 (Print) IS - 1752-8054 (Linking) VI - 16 IP - 8 DP - 2023 Aug TI - Pharmacokinetic and pharmacodynamic drug-drug interactions between evogliptin and empagliflozin or dapagliflozin in healthy male volunteers. PG - 1469-1478 LID - 10.1111/cts.13566 [doi] AB - Evogliptin (EV) is a novel dipeptidyl peptidase-4 inhibitor (DPP4i) for glycemic control in patients with type 2 diabetes mellitus (T2DM). This study evaluated the pharmacokinetic (PK) and pharmacodynamic (PD) interactions between EV and sodium glucose cotransporter-2 inhibitors (SGLT2i) in healthy volunteers since combination therapy of DPP4i and SGLT2i has been considered as an effective option for T2DM treatment. A randomized, open-label, multiple-dose, two-arm, three-period, three treatments, two-sequence crossover study was conducted in healthy Korean volunteers. In arm 1, subjects were administered 5 mg of EV once daily for 7 days, 25 mg of empagliflozin (EP) once daily for 5 days, and the combination once daily for 5 days (EV + EP). In arm 2, subjects were administered 5 mg of EV once daily for 7 days, 10 mg of dapagliflozin (DP) once daily for 5 days, and the combination once daily for 5 days (EV + DP). Serial blood samples were collected for PK analysis, and oral glucose tolerance tests were conducted for PD analysis. In each arm, a total of 18 subjects completed the study. All adverse events (AEs) were mild with no serious AEs. The geometric mean ratio and confidence interval of the main PK parameters (maximum concentration of the drug in plasma at steady state and area under the plasma drug concentration-time curve within a dosing interval at a steady state) between EV and either EP or DP alone were not significantly altered by co-administration. Administration of EV + EP or EV + DP did not result in significant PD changes, as determined by the glucose-lowering effect. Administration of EV + EP or EV + DP had no significant effects on the PK profiles of each drug. All treatments were well-tolerated. CI - (c) 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. FAU - Kim, Dasohm AU - Kim D AUID- ORCID: 0000-0002-7925-194X AD - Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. AD - Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of Medicine and Pharmacy, Yonsei University, Incheon, South Korea. FAU - Choi, Minkyu AU - Choi M AUID- ORCID: 0000-0003-2407-0057 AD - Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. AD - Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of Medicine and Pharmacy, Yonsei University, Incheon, South Korea. FAU - Jin, Byung Hak AU - Jin BH AUID- ORCID: 0000-0002-8655-4076 AD - Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. AD - Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of Medicine and Pharmacy, Yonsei University, Incheon, South Korea. FAU - Hong, Taegon AU - Hong T AUID- ORCID: 0000-0001-7490-0085 AD - Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. FAU - Kim, Choon Ok AU - Kim CO AUID- ORCID: 0000-0002-2319-1108 AD - Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. FAU - Yoo, Byung Won AU - Yoo BW AUID- ORCID: 0000-0001-6895-1484 AD - Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. FAU - Park, Min Soo AU - Park MS AUID- ORCID: 0000-0002-4395-9938 AD - Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. AD - Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of Medicine and Pharmacy, Yonsei University, Incheon, South Korea. AD - Department of Pediatrics, Yonsei University College of Medicine, Seoul, South Korea. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230621 PL - United States TA - Clin Transl Sci JT - Clinical and translational science JID - 101474067 RN - HDC1R2M35U (empagliflozin) RN - 1ULL0QJ8UC (dapagliflozin) RN - 0 (4-(3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl)piperazin-2-one) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy MH - Healthy Volunteers MH - Cross-Over Studies MH - Hypoglycemic Agents/adverse effects MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects MH - Drug Interactions PMC - PMC10432875 COIS- The authors declared no competing interests for this work. EDAT- 2023/06/07 06:42 MHDA- 2023/08/18 06:43 PMCR- 2023/06/21 CRDT- 2023/06/07 02:14 PHST- 2023/05/19 00:00 [revised] PHST- 2023/03/24 00:00 [received] PHST- 2023/05/27 00:00 [accepted] PHST- 2023/08/18 06:43 [medline] PHST- 2023/06/07 06:42 [pubmed] PHST- 2023/06/07 02:14 [entrez] PHST- 2023/06/21 00:00 [pmc-release] AID - CTS13566 [pii] AID - 10.1111/cts.13566 [doi] PST - ppublish SO - Clin Transl Sci. 2023 Aug;16(8):1469-1478. doi: 10.1111/cts.13566. Epub 2023 Jun 21.