The effect of aleglitazar on the pharmacokinetics and pharmacodynamics of S- and R-warfarin in healthy male subjects

Journal of Cardiovascular Pharmacology

Volumn 63, Issue 2, 2014, Pages 152-157

  Sanwald Ducray, Patricia ^a   Jamois, Candice ^a   Banken, Ludger ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

Aleglitazar; Drugdrug interaction; PPAR; Type 2 diabetes; Warfarin

Indexed keywords

ANTICOAGULANTS; AREA UNDER CURVE; CROSS-OVER STUDIES; DRUG INTERACTIONS; FACTOR VII; HUMANS; MALE; OXAZOLES; PPAR ALPHA; PPAR GAMMA; PROTHROMBIN TIME; STEREOISOMERISM; THIOPHENES; WARFARIN; YOUNG ADULT;

EID: 84894025914     PISSN: 01602446     EISSN: 15334023     Source Type: Journal    
DOI: 10.1097/FJC.0000000000000033     Document Type: Article

References (22)

1. World Health Organization. Diabetes Fact Sheet 312. 2011. Available at: Http://www.who.int/mediacentre/factsheets/fs312/en/. Accessed November 1, 2013
2. Ginsberg HN, Maccallum PR. The obesity, metabolic syndrome, and type 2 diabetes mellitus pandemic: Part I. Increased cardiovascular disease risk and the importance of atherogenic dyslipidemia in persons with the metabolic syndrome and type 2 diabetes mellitus. J Cardiometab Syndr. 2009;4:113-119
3. Lalloyer F, Staels B. Fibrates, glitazones, and peroxisome proliferatoractivated receptors. Arterioscler Thromb Vasc Biol. 2010;30:894-899
4. Henry RR, Lincoff AM, Mudaliar S, et al. Effect of the dual peroxisome proliferator-Activated receptor-Alpha/gamma agonist aleglitazar on risk of cardiovascular disease in patients with type 2 diabetes (SYNCHRONY): A phase II, randomised, dose-ranging study. Lancet. 2009;374:126-135
5. Toon S, Hopkins KJ, Garstang FM. Enoxacin-warfarin interaction: Pharmacokinetic and stereochemical aspects. Clin Pharmacol Ther. 1987;42 (suppl):33-41
6. Hirsh J. AHA/ACC foundation guide to warfarin therapy. Circulation. 2003;107:1692-1711
7. Tsao J. Effect of albumin on hepatic uptake of warfarin in normal and analbuminemic mutant rats: Analysis by multiple indicator dilution method. J Pharmacokinet Biopharm. 1986;14:51-64
8. Sturm S, Seiberling M, Weick I, et al. Metabolism, excretion, and pharmacokinetics of [14C]- radiolabeled aleglitazar: A phase I, non-randomized, open-label, single-center, single-dose study of metabolism, excretion and pharmacokinetics of 14C-radiolabeled aleglitazar in healthy male volunteers. Clin Ther. 2012;34:420-429
9. Redman AR. Implication of cytochrome P450 2C9 polymorphism on warfarin metabolism and dosing. Pharmacotherapy. 2011;21:235-242
10. Daly AK, King BP. Pharmacogenetics of oral anticoagulants. Pharmacogenetics. 2003;13:247-252
11. Sanwald-Ducray P, Liogier Dardhuy X, et al. Pharmacokinetics, pharmacodynamics, and tolerability of aleglitazar in patients with type 2 diabetes: Results from a randomized, placebo-controlled clinical study. Clin Pharmacol Ther. 2010;88:197-203
12. Deehan R, Maerz-Weiss P, Catlett NL, et al. Comparative transcriptional network modeling of three PPAR-Alpha/gamma co-Agonists reveals distinct metabolic gene signatures in primary human hepatocytes. PLoS One. 2012;7:e35012
13. Camm AJ. 2012 focused update of the ESC guidelines for the management of atrial fibrillation. Eur Heart J. 2012;33:2719-2747
14. Wright RS, Anderson JL, Adams CD, et al. 2011 ACCF/AHA focused update incorporated into the ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: A report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice guidelines developed in collaboration with the American Academy of Family Physicians, Society for cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons. J Am Coll Cardiol. 2011;57:e215-e367
15. Cochran KA. Bleeding incidence with concomitant use of antidepressants and warfarin. Ther Drug Monit. 2011;33:433-438
16. Bell WR. Acetaminophen and warfarin: Undesirable synergy. JAMA. 1998;79:702-703
17. OReilly RA. Stereoselective interaction of trimethoprim-sulfamethoxazole with the separated enantiomorphs of racemic warfarin in man. N Engl J Med. 1980;302:33-35
18. OReilly RA. The stereoselective interaction of warfarin and metronidazole in man. N Engl J Med. 1976;295:354-357
19. Duncan D. Antidepressant interactions with warfarin. Int Clin Psychopharmacol. 1998;13(suppl):87-94
20. F. Hoffmann-La Roche AG. AleCardio study. A study with aleglitazar in patients with a recent acute coronary syndrome and type 2 diabetes mellitus. 2010. Available at: Http://clinicaltrials.gov/ct2/show/NCT01042769. Accessed November 1, 2013
21. Fung E, Patsopoulos NA, Belknap SM, et al. Effect of genetic variants, especially CYP2C9 and VKORC1, on the pharmacology of warfarin. Semin Thromb Hemost. 2012;38:893-904
22. F. Hoffman-La Roche AG. AleCardio [press release]. July 2013. Available at: Http://www.roche.com/media/media-releases/med-cor-2013-07-10.htm/. Accessed November 1, 2013