Vildagliptin, a novel dipeptidyl peptidase IV inhibitor, has no pharmacokinetic interactions with the antihypertensive agents amlodipine, valsartan, and ramipril in healthy subjects

Journal of Clinical Pharmacology

Volumn 48, Issue 1, 2008, Pages 85-95

  He, Yan Ling ^a   Ligueros Saylan, Monica ^b   Sunkara, Gangadhar ^b   Sabo, Ron ^b   Zhao, Charlie ^b   Yibin Wang, ^b   Campestrini, Joelle ^c   Pommier, Francoise ^c   Dole, Kiran ^b   Marion, Alan ^d   Dole, William P ^a   Howard, Dan ^b  

^a NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^b NOVARTIS PHARMA AG   (Switzerland)

^c NOVARTIS PHARMA K K   (Japan)

^d MDS Inc   (Canada)

Author keywords

Angiotensin converting enzyme inhibitor; Angiotensin receptor blocker; Calcium channel blocker; Dipeptidyl peptidase IV inhibitor; Pharmacokinetics; Type 2 diabetes; Vildagliptin

Indexed keywords

AMLODIPINE; ANTIHYPERTENSIVE AGENT; CREATINE KINASE; DIPEPTIDYL PEPTIDASE IV INHIBITOR; GAMMA GLUTAMYLTRANSFERASE; RAMIPRIL; VALSARTAN; VILDAGLIPTIN;

ABDOMINAL DISCOMFORT; ADULT; AREA UNDER THE CURVE; ARTICLE; BIOEQUIVALENCE; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; CONFIDENCE INTERVAL; CONSTIPATION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CREATINE KINASE BLOOD LEVEL; CROSSOVER PROCEDURE; DECREASED APPETITE; DIARRHEA; DIZZINESS; DRUG BLOOD LEVEL; DRUG INDUCED HEADACHE; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPEPSIA; FACE EDEMA; FEMALE; FLATULENCE; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; HUMAN; HYPERTENSION; MALE; MONOTHERAPY; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; NORMAL HUMAN; NOSE CONGESTION; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SOMNOLENCE; STEADY STATE;

ADAMANTANE; ADMINISTRATION, ORAL; ADULT; AMLODIPINE; ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; ANTIHYPERTENSIVE AGENTS; AREA UNDER CURVE; CROSS-OVER STUDIES; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; DRUG INTERACTIONS; FEMALE; HALF-LIFE; HEADACHE; HUMANS; MALE; MIDDLE AGED; NAUSEA; NITRILES; PYRROLIDINES; RAMIPRIL; TABLETS; TETRAZOLES; VALINE;

EID: 37349024818     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1177/0091270007307880     Document Type: Article

References (26)

1. Tarnow L., Rossing P., Gall MA, Nielsen FS, Parving HH Prevalence of arterial hypertension in diabetic patients before and after the JNC-V. Diabetes Care. 1994 ; 17: 1247-1251.
2. Stamler J., Vaccaro O., Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993 ; 16: 434-444.
3. Klag MJ, Whelton PK, Randall BL, et al. Blood pressure and end-stage renal disease in men. N Engl J Med. 1996 ; 334: 13-18.
4. Brancati FL, Whelton PK, Randall BL, Neaton JD, Stamler J., Klag MJ Risk of end-stage renal disease in diabetes mellitus: a prospective cohort study of men screened for MRFIT. Multiple Risk Factor Intervention Trial. JAMA. 1997 ; 278: 2069-2074.
5. Sowers JR, Epstein M., Frohlich ED Diabetes, hypertension, and cardiovascular disease: an update. Hypertension. 2001 ; 37: 1053-1059.
6. Turnbull F., Neal B., Algert C., et al. Effects of different blood pressure-lowering regimens on major cardiovascular events in individuals with and without diabetes mellitus: results of prospectively designed overviews of randomized trials. Arch Intern Med. 2005 ; 165: 1410-1419.
7. Heart Outcomes Prevention Evaluation Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet. 2000 ; 355: 253-259.
8. Allhat Investigators. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002 ; 288: 2981-2997.
9. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998 ; 317: 703-713.
10. Johnson ML, Singh H. Patterns of antihypertensive therapy among patients with diabetes. J Gen Intern Med. 2005 ; 20: 842-846.
11. Holst JJ, Deacon CF Inhibition of the activity of dipeptidyl-peptidase IV as a treatment for type 2 diabetes. Diabetes. 1998 ; 47: 1663-1670.
12. Mentlein R. Dipeptidyl-peptidase IV (CD26)-role in the inactivation of regulatory peptides. Regul Pept. 1999 ; 85: 9-24.
13. Kieffer TJ, Habener JF The glucagon-like peptides. Endocrine Rev. 1999 ; 20: 876-913.
14. Drucker DJ The biology of incretin hormones. Cell Metab. 2006 ; 3: 153-165.
15. Ahren 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.
16. Mari A., Sallas WM, He YL, et al. Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes. J Clin Endocrinol Metab. 2005 ; 90: 4888-4894.
17. He YL, Sabo R., Balez S., et al. Absolute bioavailability of vildagliptin in healthy subjects. Clin Pharmacol Ther. 2006 ; 79: P38.
18. He YL, Balch A., Campestrini J., et al. Pharmacokinetics and pharmacodynamics of the DPP-4 inhibitor, LAF237, in patients with type 2 diabetes. Clin Pharmacol Ther. 2005 ; 77: P56.
19. He YL, Wang Y., Bullock J., et al. Pharmacodynamics of vildagliptin in patients with type 2 diabetes during OGTT. J Clin Pharmacol. 2007 ; 47: 633-641.
20. Darvari R., Boroujerdi M. Concentration dependency of modulatory effect of amlodipine on P-glycoprotein efflux activity of doxorubicin-a comparison with tamoxifen. J Pharm Pharmacol. 2004 ; 56: 985-991.
21. Katoh M., Nakajima M., Yamazaki H., Yokoi T. Inhibitory potencies of 1,4-dihydropyridine calcium antagonists to P-glycoprotein-mediated transport: comparison with the effects on CYP3A4. Pharm Res. 2000 ; 17: 1189-1197.
22. Drobitch RK, McLellan RA, Renton KW Amlodipine inhibits rat microsomal cytochrome P450-mediated drug biotransformation. J Pharm Sci. 1997 ; 86: 1501-1503.
23. Waldmeier F., Flesch G., Muller P., et al. Pharmacokinetics, disposition and biotransformation of [14C]-radiolabelled valsartan in healthy male volunteers after a single oral dose. Xenobiotica. 1997 ; 27: 59-71.
24. Nakashima A., Kawashita H., Masuda N., et al. Identification of cytochrome P450 forms involved in the 4-hydroxylation of valsartan, a potent and specific angiotensin II receptor antagonist, in human liver microsomes. Xenobiotica. 2005 ; 35: 589-602.
25. Vasmant D., Bender N. The renin-angiotensin system and ramipril, a new converting enzyme inhibitor. J Cardiovasc Pharmacol. 1989 ; 14 (suppl 4). S46 - S52.
26. Ristic S., Byiers S., Foley J., Holmes D. Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response. Diabetes Obes Metab. 2005 ; 7: 692-698.