Pharmacokinetics, pharmacodynamics and tolerability of multiple oral doses of linagliptin, a dipeptidyl peptidase-4 inhibitor in male type 2 diabetes patients

Diabetes, Obesity and Metabolism

Volumn 11, Issue 8, 2009, Pages 786-794

  Heise, T ^a   Graefe Mody, E U ^b   Huttner S ^b   Ring, S ^b   Trommeshauser, D ^b   Dugi, Klaus A ^b  

^a PROFIL Institut für Stoffwechselforschung   (Germany)

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

Author keywords

DPP 4; Glycaemic control; Linagliptin; Pharmacokinetics; Safety

Indexed keywords

8 (3 AMINO 1 PIPERIDINYL) 7 (2 BUTYNYL) 3 METHYL 1 (4 METHYL 2 QUINAZOLINYLMETHYL)XANTHINE; HEMOGLOBIN A1C; PLACEBO;

ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG ACCUMULATION; DRUG BLOOD LEVEL; DRUG DOSE INCREASE; DRUG EXCRETION; DRUG FATALITY; DRUG HALF LIFE; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG URINE LEVEL; ELECTROCARDIOGRAM; ENZYME ACTIVITY; ENZYME INHIBITION; GLYCEMIC CONTROL; HUMAN; HYPOGLYCEMIA; LABORATORY TEST; MALE; MAXIMUM PLASMA CONCENTRATION; MULTICENTER STUDY; MULTIPLE DRUG DOSE; NON INSULIN DEPENDENT DIABETES MELLITUS; ORAL GLUCOSE TOLERANCE TEST; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADMINISTRATION, ORAL; ADULT; AREA UNDER CURVE; DIABETES MELLITUS, TYPE 2; DIPEPTIDYL PEPTIDASE 4; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; HALF-LIFE; HUMANS; MALE; METABOLIC CLEARANCE RATE; MIDDLE AGED; PURINES; QUINAZOLINES; YOUNG ADULT;

EID: 67649998759     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/j.1463-1326.2009.01046.x     Document Type: Article

References (36)

1. Ahrén B. Gut peptides and type 2 diabetes mellitus treatment. Curr Diab Rep 2003; 3: 365-372.
2. Drucker DJ. Therapeutic potential of dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes. Expert Opin Investig Drugs 2003; 12: 87-100.
3. Deacon CF. Therapeutic strategies based on glucagon-like peptide 1. Diabetes 2004; 53: 2181-2189.
4. Deacon CF. What do we know about the secretion and degradation of incretin hormones? Regul Pept 2005; 128: 117-124.
5. Idris I, Donnelly R. Dipeptidyl peptidase-IV inhibitors: A major new class of oral antidiabetic drug. Diabetes Obes Metab 2007; 9: 153-165.
6. Ahrén B, Landin-Olsson M, Jansson PA, Svensson M, Holmes D, Schweizer A. Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. J Clin Endocrinol Metab 2004; 89: 2078-2084.
7. Ahrén B, Gomis R, Standl E, Mills D, Schweizer A. Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care 2004; 27: 2874-2880.
8. Pratley RE, Salsali A. Inhibition of DPP-4: A new therapeutic approach for the treatment of type 2 diabetes. Curr Med Res Opin 2007; 23: 919-931.
9. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA 2002; 287: 360-372.
10. Reimer MK, Hoist JJ, Ahrén B. Long-term inhibition of dipeptidyl peptidase IV improves glucose tolerance and preserves islet function in mice. Eur J Endocrinol 2002; 146: 717-727.
11. Ahrén B, Pacini G, Foley JE, Schweizer A. Improved meal-related β-cell function and insulin sensitivity by the dipeptidyl peptidase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year. Diabetes Care 2005; 28: 1936-1940.
12. Mari A, Sallas WM, He YL et al. Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed β-Cell function in patients with type 2 diabetes. J Clin Endocrinol Metab 2005; 90: 4888-4894.
13. Drucker DJ. Enhancing incretin action for the treatment of type 2 diabetes. Diabetes Care 2003; 26: 2929-2940.
14. Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD. Effect of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 2004; 27: 2628-2635.
15. Thomas L, Eckhardt M, Langkopf E, Tadayyon M, Himmelsbach F, Mark M. (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl -quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action compared with other dipeptidyl peptidase-4 inhibitors. J Pharmacol Exp Ther 2008; 325: 175-182.
16. 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.
17. World Medical Association. Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Patients. 59th WMA General Assembly, Seoul, October 2008. World Medical Association. France.
18. Hoffman D, Kringle R, Lockwoos G, Turpault S, Yow E, Mathieu G. Nonlinear mixed effects modelling for estimation of steady state attainment. Pharm Stat 2005; 4: 15-24.
19. He YL, Wang Y, Bullock JM et al. Pharmacodynamics of vildagliptin in patients with type 2 diabetes during OGTT. J Clin Pharmacol 2007; 47: 633-641.
20. He YL, Sabo R, Campestrini J et al. The effect of age, gender, and body mass index on the pharmacokinetics and pharmacodynamics of vildagliptin in healthy volunteers. Br J Clin Pharmacol 2008; 65: 338-346.
21. He YL, Serra D, Wang Y et al. Pharmacokinetics and pharmacodynamics of vildagliptin in patients with type 2 diabetes mellitus. Clin Pharmacokinet 2007; 46: 577-588.
22. O'Farrell AM, van Vliet A, Abou Farha K et al. Pharmacokinetic and pharmacodynamic assessments of the dipeptidyl peptidase-4 inhibitor PHX1149: Double-blind, placebo-controlled, single- and multiple-dose studies in healthy subjects. Clin Ther 2007; 29: 1692-1705.
23. Bergman AJ, Stevens C, Zhou Y et al. Pharmacokinetic and pharmacodynamic properties of multiple oral doses of sitagliptin, a dipeptidyl peptidase-IV inhibitor: A double-blind, randomized, placebo-controlled study in healthy male volunteers. Clin Ther 2006; 28: 55-72.
24. Herman GA, Bergman A, Stevens C et al. Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes. J Clin Endocrinol Metab 2006; 91: 4612-4619.
25. Bosi E, Camisasca RP, Collober C, Rochotte E, Garber AJ. Effects of vildagliptin on glucose control over 24 weeks in patients with type 2 diabetes inadequately controlled with metformin. Diabetes Care 2007; 30: 890-895.
26. Scherbaum WA, Schweizer A, Mari A et al. Efficacy and tolerability of vildagliptin in drug-naïve patients with type 2 diabetes and mild hyperglycaemia. Diabetes Obes Metab 2008; 10: 675-682.
27. Charbonnel B, Karasik A, Liu J, Wu M, Meininger G. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care 2006; 29: 2638-2643.
28. Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C, Williams-Herman DE. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care 2006; 29: 2632-2637.
29. Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: A randomized, double-blind, non-inferiority trial. Diabetes Obes Metab 2007; 9: 194-205.
30. He YL, Sadler BM, Sabo R et al. The absolute oral bioavailability and population-based pharmacokinetic modelling of a novel dipeptidyl peptidase-IV inhibitor, vildagliptin, in healthy volunteers. Clin Pharmacokinet 2007; 46: 787-802.
31. Herman GA, Stevens C, Van Dyck K et al. Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: Results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clin Pharmacol Ther 2005; 78: 675-688.
32. Christopher R, Covington P, Davenport M et al. Pharmacokinetics, pharmacodynamics, and tolerability of single increasing doses of the dipeptidyl peptidase-4 inhibitor alogliptin in healthy male subjects. Clin Ther 2008; 30: 513-527.
33. Covington P, Christopher R, Davenport M et al. Pharmacokinetic, pharmacodynamic, and tolerability profiles of the dipeptidyl peptidase-4 inhibitor alogliptin: A randomized, double-blind, placebo-controlled, multiple-dose study in adult patients with type 2 diabetes. Clin Ther 2008; 30: 499-512.
34. Ritz E, Rychlik I, Locatelli F, Halimi S. End-stage renal failure in type 2 diabetes: A medical catastrophe of worldwide dimensions. Am J Kidney Dis 1999; 34: 795-808.
35. Kramer HJ, Nguyen QD, Curhan G, Hsu CY. Renal insufficiency in the absence of albuminuria and retinopathy among adults with type 2 diabetes mellitus. JAMA 2003; 289: 3273-3277.
36. Fuchs H, Tillement JP, 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.