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

Diabetes, Obesity and Metabolism

Volumn 13, Issue 10, 2011, Pages 939-946

  Graefe Mody, Ulrike ^a   Friedrich, C ^a   Port, A ^a   Ring, A ^a   Retlich, S ^a   Heise, T ^b   Halabi, A ^c   Woerle, H J ^a  

^a BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

^b Profil Institut fuer Stoffwechselforschung GmbH   (Germany)

^c CRS Clinical Research Services Kiel GmbH   (Germany)

Author keywords

DPP 4 inhibitor; End stage renal disease; Linagliptin; Renal impairment; Type 2 diabetes mellitus

Indexed keywords

CREATININE; DIPEPTIDYL PEPTIDASE IV; LINAGLIPTIN;

ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; CREATININE CLEARANCE; DIARRHEA; DISEASE SEVERITY; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EXCRETION; DRUG EXPOSURE; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG TOLERABILITY; DRUG URINE LEVEL; FATIGUE; FEMALE; HUMAN; KIDNEY DYSFUNCTION; KIDNEY FAILURE; KIDNEY FUNCTION; MALE; MAXIMUM PLASMA CONCENTRATION; NON INSULIN DEPENDENT DIABETES MELLITUS; PLASMA CONCENTRATION-TIME CURVE; STEADY STATE; TIME TO MAXIMUM PLASMA CONCENTRATION; URINARY EXCRETION;

EID: 80052530183     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/j.1463-1326.2011.01458.x     Document Type: Article

References (21)

1. Bakris GL. Recognition, pathogenesis, and treatment of different stages of nephropathy in the type 2 diabetes mellitus patient. Mayo Clin Proc 2011; 86: 444-456.
2. Scheen AJ. Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab 2010; 12: 648-658.
3. Blech S, Ludwig-Schwellinger E, Gräfe-Mody EU, Withopf B, Wagner K. The metabolism and disposition of the oral dipeptidyl peptidase-4 inhibitor, linagliptin, in humans. Drug Metab Dispos 2010; 38: 667-678.
4. Food and Drug Administration. Guidance for Industry. Pharmacokinetics in Patients with Impaired Renal Function-Study Design, Data Analysis, and Impact on Dosing and Labeling. Rockville: U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER) [Revision 1; March 2010]. Available from URL: Accessed 11 February 2011.
5. Committee for Medicinal Products for Human Use. Note for Guidance on the Evaluation of the Pharmacokinetics of Medicinal Products in Patients with Impaired Renal Function. 23 June 2004. London: European Medicines Agency, 2004. Available from URL: Accessed 11 February 2011.
6. Heise T, Graefe-Mody EU, Hüttner S, Ring A, Trommeshauser D, Dugi KA. Pharmacokinetics, pharmacodynamics and tolerability of multiple oral doses of linagliptin, a dipeptidyl peptidase-4 inhibitor in male type 2 diabetes patients. Diabetes Obes Metab 2009; 11: 786-794.
7. Hüttner S, Graefe-Mody EU, Withopf B, Ring A, Dugi KA. Safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of BI 1356, an inhibitor of dipeptidyl peptidase 4, in healthy male volunteers. J Clin Pharmacol 2008; 48: 1171-1178.
8. Retlich S, Duval V, Graefe-Mody U, Jaehde U, Staab A. Impact of target-mediated drug disposition on linagliptin pharmacokinetics and DPP-4 inhibition in type 2 diabetic patients. J Clin Pharmacol 2010; 50: 873-885.
9. Fuchs H, Tillement J-P, Urien S, Greischel A, Roth W. Concentration-dependent plasma protein binding of the novel dipeptidyl peptidase 4 inhibitor BI 1356 due to saturable binding to its target in plasma of mice, rats and humans. J Pharm Pharmacol 2009; 61: 55-62.
10. Friedrich C, Emser A, Woerle H-J, Graefe-Mody U. Renal impairment has no relevant effect on long-term exposure of linagliptin in patients with type 2 diabetes mellitus. Diabetes 2011; 60: A303.
11. Graefe-Mody U, Rose P, Ring A, Waldhauser L, Cinca R, Woerle H-J. The novel DPP-4 inhibitor linagliptin can be administered to patients with various degrees of hepatic impairment without dose adjustment. J Diabetes 2011; 3(Suppl. 1): 220 [Abstract].
12. Ring A, Port A, Graefe-Mody EU, Revollo I, Iovino M, Dugi KA. The DPP-4 inhibitor linagliptin does not prolong the QT interval at therapeutic and supratherapeutic doses. Br J Clin Pharmacol 2011; 72: 39-50.
13. 14C]sitagliptin in humans. Drug Metab Dispos 2007; 35: 533-538.
14. Sharma MD. Role of saxagliptin as monotherapy or adjunct therapy in the treatment of type 2 diabetes. Ther Clin Risk Manag 2010; 6: 233-237.
15. Novartis Europharm Limited. Galvus®50 mg tablets. Summary of product characteristics. 24 January 2011. Available from URL: Accessed 18 April 2011.
16. European Medicines Agency (EMEA). Galvus (vildagliptin). European Public Assessment Report (EPAR). Scientific discussion. 2007. London: European Medicines Agency, 2007. Available from URL: Accessed 18 April 2011.
17. Bergman AJ, Cote J, Yi B et al. Effect of renal insufficiency on the pharmacokinetics of sitagliptin, a dipeptidyl peptidase-4 inhibitor. Diabetes Care 2007; 30: 1862-1864.
18. Boulton DW, Li L, Frevert EU et al. Influence of renal or hepatic impairment on the pharmacokinetics of saxagliptin. Clin Pharmacokinet 2011; 50: 253-265.
19. Bristol-Myers Squibb Company. ONGLYZA™(saxagliptin) tablets. Prescribing information. February 2011. Available from URL: Accessed 15 March 2011.
20. Merck Sharp & Dohme Corp a subsidiary of Merck & Co., Inc. JANUVIA®(sitagliptin) tablets. Prescribing information. April 2011. Available from URL: Accessed 18 April 2011.
21. Nowicki M, Rychlik I, Haller H, Warren ML, Suchower L, Gause-Nilsson I. Saxagliptin improves glycaemic control and is well tolerated in patients with type 2 diabetes mellitus and renal impairment. Diabetes Obes Metab 2011; 13: 523-532.