Effect of Renal Impairment on the Pharmacokinetics of the Dipeptidyl Peptidase-4 Inhibitor Linagliptin.
Summary of "Effect of Renal Impairment on the Pharmacokinetics of the Dipeptidyl Peptidase-4 Inhibitor Linagliptin."
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 (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 post-dosing 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 only has a minor effect on linagliptin pharmacokinetics. Consequently, there will be no need for adjusting the linagliptin dose in renally impaired patients with T2DM.
Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany Profil Institut fuer Stoffwechselforschung GmbH, Neuss, Germany CRS Clinical Research Services Kiel GmbH, Kiel, Germany.
This article was published in the following journal.
Name: Diabetes, obesity & metabolism
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21672124
- DOI: http://dx.doi.org/10.1111/j.1463-1326.2011.01458.x
Medical and Biotech [MESH] Definitions
Dipeptidyl Peptidase 4
A serine protease that catalyses the release of an N-terminal dipeptide. Several biologically-active peptides have been identified as dipeptidyl peptidase 4 substrates including INCRETINS; NEUROPEPTIDES; and CHEMOKINES. The protein is also found bound to ADENOSINE DEAMINASE on the T-CELL surface and is believed to play a role in T-cell activation.
Dipeptidyl-peptidase Iv Inhibitors
Compounds that supress the degradation of INCRETINS by blocking the action of DIPEPTIDYL-PEPTIDASE IV. This helps to correct the defective INSULIN and GLUCAGON secretion characteristic of TYPE 2 DIABETES MELLITUS by stimulating insulin secretion and suppressing glucagon release.
Cell-surface glycoproteins and serine protease, also known as dipeptidyl-peptidase IV, that plays a role in T-lymphocyte activation. CD26 binds to ADENOSINE DEAMINASE on the T-cell surface.
The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy.
Secretory Leukocyte Peptidase Inhibitor
A proteinase inhibitor found in various BODILY SECRETIONS that coat mucosal surfaces such as SEMINAL PLASMA; CERVICAL MUCUS; and bronchial secretions. It plays a role in protecting epithelial tissues from LEUKOCYTE-derived serine proteases such as NEUTROPHIL ELASTASE.
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