Effect of renal impairment on the pharmacokinetics of the dipeptidyl peptidase-4 inhibitor linagliptin

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2011-10, Vol.13 (10), p.939-946
• Main Authors: Graefe-Mody, U., Friedrich, C., Port, A., Ring, A., Retlich, S., Heise, T., Halabi, A., Woerle, H.-J.
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Area Under Curve; Creatinine; Creatinine - metabolism; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetic Nephropathies - metabolism; Dipeptidyl-Peptidase IV Inhibitors - administration & dosage; Dipeptidyl-Peptidase IV Inhibitors - pharmacokinetics; Dose-Response Relationship, Drug; DPP-4 inhibitor; end-stage renal disease; Excretion; Female; Half-Life; Humans; Kidney Failure, Chronic - metabolism; Linagliptin; Male; Middle Aged; Pharmacokinetics; Purines - administration & dosage; Purines - pharmacokinetics; Quinazolines - administration & dosage; Quinazolines - pharmacokinetics; Renal function; renal impairment; Treatment Outcome; type 2 diabetes mellitus
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/j.1463-1326.2011.01458.x

Aim: This study assessed the influence of various degrees of renal impairment on the exposure of linagliptin, a dipeptidyl peptidase‐4 (DPP‐4) inhibitor with a primarily non‐renal route of excretion, in subjects with type 2 diabetes mellitus (T2DM). Methods: Linagliptin pharmacokinetics was studied under single‐dose and steady‐state conditions in subjects with mild, moderate and severe renal impairment (with and without T2DM) and end‐stage renal disease and compared with the pharmacokinetics in subjects with normal renal function (with and without T2DM). Results: Renal excretion of unchanged linagliptin was