title: Effect of renal impairment on the pharmacokinetics of the dipeptidyl peptidase-4 inhibitor linagliptin(*).
abstract: OBJECTIVE
  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 <7% in all groups. Under single-dose conditions, the degree of renal impairment did not affect mean plasma linagliptin concentration-time profiles. These showed a similar decline and almost identical plasma concentrations 24 h postdosing in subjects with mild, moderate or severe renal impairment and in subjects with T2DM with and without renal impairment. Although there was a tendency towards slightly higher (20-60%) exposure in renally impaired subjects (with and without T2DM) compared with subjects with normal renal function, the steady-state AUC and C(max) values showed a large overlap and were not affected by the degree of renal impairment. The accumulation half-life of linagliptin ranged from 14-15 h in subjects with normal renal function to 18 h in severe renal impairment. Only a weak correlation (r(2) = 0.18) was seen between creatinine clearance and steady-state exposure.
  
  
  CONCLUSIONS
  Renal impairment has only a minor effect on linagliptin pharmacokinetics. Consequently, there will be no need for adjusting the linagliptin dose in renally impaired patients with T2DM.
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany. Ulrike.Graefe-Mody@boehringer-ingelheim.com
authors.forename: U
authors.initials: U
authors.lastname: Graefe-Mody
authors.forename: C
authors.initials: C
authors.lastname: Friedrich
authors.forename: A
authors.initials: A
authors.lastname: Port
authors.forename: A
authors.initials: A
authors.lastname: Ring
authors.forename: S
authors.initials: S
authors.lastname: Retlich
authors.forename: T
authors.initials: T
authors.lastname: Heise
authors.forename: A
authors.initials: A
authors.lastname: Halabi
authors.forename: H-J
authors.initials: HJ
authors.lastname: Woerle
mesh_terms: D000704:Analysis of Variance; D019540:Area Under Curve; D003404:Creatinine / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D000069476:Linagliptin; D008297:Male; D008875:Middle Aged; D011687:Purines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011799:Quinazolines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D011687:Purines; D011799:Quinazolines; D000069476:Linagliptin; D003404:Creatinine