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 (Cmax ) and overall exposure (AUC0-∞ ) to teneligliptin. Geometric least square mean ratios for Cmax in subjects with mild and moderate hepatic impairment were 25% and 38% higher than in healthy subjects, and those for AUC0-∞ 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.

Pharmacokinetics of Teneligliptin in Subjects With Renal Impairment.

The pharmacokinetics of teneligliptin was compared in renally impaired and healthy subjects. Subjects were assigned to one of four groups of eight subjects, according to the stage of disease [mild, moderate, severe or end stage renal disease (ESRD)], while matched healthy subjects were allocated to one of two reference groups. Mild, moderate and severe renal impairment had no effect on maximum plasma concentration (Cmax ) following a single oral dose of 20 mg teneligliptin, as defined in the FDA guideline. AUC0-∞ was increased in all groups relative to the reference group but this was unrelated to the degree of renal impairment. Mean plasma protein binding was <80% in all groups. Overall, teneligliptin was well tolerated by subjects with renal impairment or ESRD. Dialysis is not expected to affect the efficacy or safety of teneligliptin. These results indicate that dose adjustment may not be needed when teneligliptin is administered to subjects with mild, moderate or severe renal impairment or ESRD.