title: Pharmacokinetics and safety of teneligliptin in subjects with hepatic impairment.
abstract: 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.
authors.affiliation: CRS Clinical Research Services Kiel GmbH, Kiel, Germany.
authors.forename: Atef
authors.initials: A
authors.lastname: Halabi
authors.affiliation: CRS Clinical Research Services Kiel GmbH, Kiel, Germany.
authors.forename: Haidar
authors.initials: H
authors.lastname: Maatouk
authors.affiliation: CRS Clinical Research Services Mannheim GmbH, Grünstadt, Germany.
authors.forename: Karl Ernst
authors.initials: KE
authors.lastname: Siegler
authors.affiliation: CRS Clinical Research Services Mannheim GmbH, Grünstadt, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Faisst
authors.affiliation: Gastroenterologische Gemeinschaftspraxis Kiel, Kiel, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Hinrichsen
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D018570:Risk Assessment; D012720:Severity of Illness Index; D053778:Thiazolidines / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: C579035:3-(4-(4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl)pyrrolidin-2-ylcarbonyl)thiazolidine; D054873:Dipeptidyl-Peptidase IV Inhibitors; D011720:Pyrazoles; D053778:Thiazolidines
keywords: DPP-IV inhibitor; MP-513; hepatic impairment; pharmacokinetics; teneligliptin