Pharmacokinetics and safety of teneligliptin in subjects with hepatic impairment. Issue 4 (17th February 2014)

• Record Type: Journal Article
• Authors: Halabi, Atef; Maatouk, Haidar; Siegler, Karl Ernst; Faisst, Nadja; Hinrichsen, Holger
• Is Part Of: Clinical pharmacology in drug development. Volume 3:Issue 4(2014:Jul./Aug.)
• Page Start: 290
• Page End: 296
• Publication Date: 2014-02-17
• Subjects: Drugs -- Testing -- Periodicals; Drug development -- Periodicals; Clinical pharmacology -- Periodicals; 615.580724
• DOI: 10.1002/cpdd.89
• Languages: English
• ISSNs: 2160-7648

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="cpdd89-sec-0001" sec-type="section"> <p>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<sub>max</sub>) and overall exposure (AUC<sub>0–∞</sub>) to teneligliptin. Geometric least square mean ratios for C<sub>max</sub> in subjects with mild and moderate hepatic impairment were 25% and 38% higher than in healthy subjects, and those for AUC<sub>0–∞</sub> 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.</p> </sec> </abstract>