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Pharmacokinetics and safety of evogliptin in hepatically impaired patients
Author(s) -
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
Publication year - 2021
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.14680
Subject(s) - cmax , medicine , pharmacokinetics , gastroenterology , confidence interval , dipeptidyl peptidase 4 , diabetes mellitus , endocrinology , type 2 diabetes
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 ( C max ) and area under the concentration–time curve values from 0 to 120 h (AUC last ); 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 ( C max and AUC last ) 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.