Pharmacokinetics and safety of evogliptin in hepatically impaired patients

• Published in: British journal of clinical pharmacology Vol. 87; no. 7; pp. 2757 - 2766
• Main Authors: Hong, Taegon, Jin, Byung Hak, Kim, Choon Ok, Yoo, Byung Won, Kim, Dasohm, Lee, Jung Il, Kim, Beom Kyung, Ahn, Sang Hoon, Kim, Do Young, Park, Jun Yong, Park, Min Soo
• Format: Journal Article
• Language: English
• Published: England 01.07.2021
• Subjects: Area Under Curve; Diabetes Mellitus, Type 2 - drug therapy; Dipeptidyl-Peptidase IV Inhibitors - adverse effects; DPP‐4 inhibitor; evogliptin; Female; hepatic impairment; Humans; Hypoglycemic Agents - adverse effects; Liver Diseases; Male; pharmacokinetics; Piperazines; Type 2 diabetes mellitus; hepatic impairment; pharmacokinetics; Type 2 diabetes mellitus; DPP-4 inhibitor; evogliptin
• ISSN: 0306-5251; 1365-2125; 1365-2125
• DOI: 10.1111/bcp.14680

Aims Evogliptin is a potent and selective dipeptidyl peptidase‐4 inhibitor for glycaemic control in patients with type 2 diabetes mellitus. Since evogliptin is mainly eliminated through hepatic metabolism, we investigated the pharmacokinetics (PKs) and safety characteristics of evogliptin in Korean patients with mild or moderate hepatic impairment. Methods An open‐label, parallel‐group study was conducted in patients with mild or moderate hepatic impairment and healthy control subjects matched to each patient for sex, age and body mass index. A single dose (5 mg) of evogliptin was administered orally, and serial blood samples were collected over 120 h to assess the PK profile of evogliptin and its main metabolites (M7 and M8). Results Patients with mild hepatic impairment and their matched healthy controls showed similar maximum concentration (Cmax) and area under the concentration–time curve values from 0 to 120 h (AUClast); the geometric mean ratio (GMR) and 90% confidence interval (CI) were 1.04 (0.80, 1.35) and 1.01 (0.90, 1.14), respectively. Exposure to evogliptin (Cmax and AUClast) was increased by about 40% in patients with moderate hepatic impairment—the GMR and 90% CI were 1.37 (1.09, 1.72) and 1.44 (1.18, 1.75), respectively. The metabolic ratios of M7 and M8 were lower in patients with moderate hepatic impairment than in matched healthy controls. Evogliptin was well tolerated by both patients and healthy subjects. Conclusion Although evogliptin exposure was increased in patients with moderate hepatic impairment, the increase is unlikely to affect safety and efficacy adversely, and no dose adjustment is warranted.