Pharmacokinetics and safety of teneligliptin in subjects with hepatic impairment.

The pharmacokinetics of teneligliptin was compared in 3 groups of 8 subjects assigned according to their degree of hepatic impairment (mild, moderate, or matched healthy subjects). Hepatic impairment was associated with an increase in maximal plasma concentration (C_max) and overall exposure (AUC_0-∞) to teneligliptin. Geometric least square mean ratios for C_max in subjects with mild and moderate hepatic impairment were 25% and 38% higher than in healthy subjects, and those for AUC_0-∞ were 46% and 59% higher than in healthy subjects, respectively. For both parameters, the upper limit of the 90% confidence intervals was outside the 80%-125% 'no effect' limit, but below the FDA-recommended 'dose-adjustment' boundary of 200%. The lower mean total clearance in subjects with mild (9.79 L/h) or moderate (8.57 L/h) hepatic impairment resulted in longer mean half-lives (27.9 and 30.9 hours, respectively) than in healthy subjects (clearance: 13.11 L/h, half life: 24.8 hours). Protein binding ranged between 36.9% and 47.5% in subjects with hepatic impairment and between 32.5% and 34.5% in healthy subjects. Overall, teneligliptin was well tolerated by subjects with hepatic impairment. These results may indicate that caution will be needed when administering teneligliptin to subjects with hepatic impairment. [ABSTRACT FROM AUTHOR]