Riociguat (BAY 63-2521) and warfarin: A pharmacodynamic and pharmacokinetic interaction study

Journal of Clinical Pharmacology

Volumn 51, Issue 7, 2011, Pages 1051-1060

  Frey, Reiner ^a   Mück, Wolfgang ^a   Kirschbaum, Nina ^a   Krätzschmar, Jörn ^a   Weimann, Gerrit ^a   Wensing, Georg ^a  

^a BAYER PHARMA AG   (Germany)

Author keywords

Drug interaction; riociguat (BAY 63 2521); soluble guanylate cyclase stimulator; warfarin

Indexed keywords

BLOOD CLOTTING FACTOR 10; BLOOD CLOTTING FACTOR 7; PLACEBO; PROTHROMBIN; RIOCIGUAT; WARFARIN;

ABDOMINAL PAIN; ADULT; AREA UNDER THE CURVE; ARTICLE; BLURRED VISION; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIARRHEA; DRUG BLOOD LEVEL; DRUG ELIMINATION; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG INTERACTION; DRUG SAFETY; DYSPEPSIA; FLATULENCE; HEART PALPITATION; HUMAN; HUMAN EXPERIMENT; MALE; MAXIMUM PLASMA CONCENTRATION; NAUSEA; NORMAL HUMAN; PROTHROMBIN TIME; RHINOPHARYNGITIS; SINGLE DRUG DOSE; STEADY STATE; TIME TO MAXIMUM PLASMA CONCENTRATION; VOMITING;

ADULT; ANTICOAGULANTS; BLOOD COAGULATION TESTS; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; DRUG INTERACTIONS; GUANYLATE CYCLASE; HALF-LIFE; HUMANS; MALE; MIDDLE AGED; PYRAZOLES; PYRIMIDINES; RECEPTORS, CYTOPLASMIC AND NUCLEAR; STEREOISOMERISM; WARFARIN; YOUNG ADULT;

EID: 79952638658     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1177/0091270010378119     Document Type: Article

References (35)

1. D'Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med. 1991 ; 115: 343-349
2. Evgenov OV, Pacher P, Schmidt PM, Hasko G, Schmidt HH, Stasch JP. NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential. Nat Rev Drug Discov. 2006 ; 5: 755-768
3. McLaughlin VV, McGoon MD. Pulmonary arterial hypertension. Circulation. 2006 ; 114: 1417-1431
4. Arnold WP, Mittal CK, Katsuki S, Murad F. Nitric oxide activates guanylate cyclase and increases guanosine 3,:5,-cyclic monophosphate levels in various tissue preparations. Proc Natl Acad Sci U S A. 1977 ; 74: 3203-3207
5. Schermuly RT, Stasch JP, Pullamsetti SS, et al. Expression and function of soluble guanylate cyclase in pulmonary arterial hypertension. Eur Respir J. 2008 ; 32: 881-891
6. Frey R, Muck W, Unger S, Artmeier-Brandt U, Weimann G, Wensing G. Single-dose pharmacokinetics, pharmacodynamics, tolerability, and safety of the soluble guanylate cyclase stimulator BAY 63-2521: an ascending-dose study in healthy male volunteers. J Clin Pharmacol. 2008 ; 48: 926-934
7. Grimminger F, Weimann G, Frey R, et al. First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension. Eur Respir J. 2009 ; 33: 785-792
8. Ghofrani HA, Hoeper MM, Hoeffken G, Halank M, Weimann G, Grimminger F. Riociguat dose titration in patients with chronic thromboembolic pulmonary hypertension (CTEPH) or pulmonary arterial hypertension (PAH). Am J Respir Crit Care Med. 2009 ; 179: A3337
9. Johnson SR, Granton JT, Mehta S. Thrombotic arteriopathy and anticoagulation in pulmonary hypertension. Chest. 2006 ; 130: 545-552
10. Moser KM, Fedullo PF, Finkbeiner WE, Golden J. Do patients with primary pulmonary hypertension develop extensive central thrombi?. Circulation. 1995 ; 91: 741-745
11. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004 ; 351: 1425-1436
12. McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians. J Am Coll Cardiol. 2009 ; 53: 1573-1619
13. Rubin LJ, Badesch DB. Evaluation and management of the patient with pulmonary arterial hypertension. Ann Intern Med. 2005 ; 143: 282-292
14. Barst RJ, Gibbs JS, Ghofrani HA, et al. Updated evidence-based treatment algorithm in pulmonary arterial hypertension. J Am Coll Cardiol. 2009 ; 54: S78 - S84
15. Holbrook AM, Pereira JA, Labiris R, et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005 ; 165: 1095-1106
16. Kaminsky LS, Zhang ZY. Human P450 metabolism of warfarin. Pharmacol Ther. 1997 ; 73: 67-74
17. Kirchheiner J, Brockmoller J. Clinical consequences of cytochrome P450 2C9 polymorphisms. Clin Pharmacol Ther. 2005 ; 77: 1-16
18. Takahashi H, Echizen H. Pharmacogenetics of warfarin elimination and its clinical implications. Clin Pharmacokinet. 2001 ; 40: 587-603
19. Wormhoudt LW, Commandeur JN, Vermeulen NP. Genetic polymorphisms of human N-acetyltransferase, cytochrome P450, glutathione-S-transferase, and epoxide hydrolase enzymes: relevance to xenobiotic metabolism and toxicity. Crit Rev Toxicol. 1999 ; 29: 59-124
20. Margaglione M, Colaizzo D, D'Andrea G, et al. Genetic modulation of oral anticoagulation with warfarin. Thromb Haemost. 2000 ; 84: 775-778
21. Scordo MG, Pengo V, Spina E, Dahl ML, Gusella M, Padrini R. Influence of CYP2C9 and CYP2C19 genetic polymorphisms on warfarin maintenance dose and metabolic clearance. Clin Pharmacol Ther. 2002 ; 72: 702-710
22. Wallin R, Hutson SM. Warfarin and the vitamin K-dependent gamma-carboxylation system. Trends Mol Med. 2004 ; 10: 299-302
23. Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW. Identification of the gene for vitamin K epoxide reductase. Nature. 2004 ; 427: 541-544
24. Wadelius M, Pirmohamed M. Pharmacogenetics of warfarin: current status and future challenges. Pharmacogenomics J. 2007 ; 7: 99-111
25. Limdi NA, Veenstra DL. Warfarin pharmacogenetics. Pharmacotherapy. 2008 ; 28: 1084-1097
26. Kim MJ, Huang SM, Meyer UA, Rahman A, Lesko LJ. A regulatory science perspective on warfarin therapy: a pharmacogenetic opportunity. J Clin Pharmacol. 2009 ; 49: 138-146
27. Schall R, Muller FO, Hundt HK, Duursema L, Groenewoud G, Middle MV. Study of the effect of miglitol on the pharmacokinetics and pharmacodynamics of warfarin in healthy males. Arzneimittelforschung. 1996 ; 46: 41-46
28. Rieder MJ, Reiner AP, Gage BF, et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N Engl J Med. 2005 ; 352: 2285-2293
29. Barst RJ. Sitaxsentan: a selective endothelin-A receptor antagonist, for the treatment of pulmonary arterial hypertension. Expert Opin Pharmacother. 2007 ; 8: 95-109
30. Weber C, Banken L, Birnboeck H, Schulz R. Effect of the endothelin-receptor antagonist bosentan on the pharmacokinetics and pharmacodynamics of warfarin. J Clin Pharmacol. 1999 ; 39: 847-854
31. Croom KF, Curran MP. Sildenafil: a review of its use in pulmonary arterial hypertension. Drugs. 2008 ; 68: 383-397
32. Oberwittler H, Hirschfeld-Warneken A, Wesch R, et al. Significant pharmacokinetic and pharmacodynamic interaction of warfarin with the NO-independent sGC activator HMR1766. J Clin Pharmacol. 2007 ; 47: 70-77
33. Stasch JP, Hobbs AJ. NO-independent, haem-dependent soluble guanylate cyclase stimulators. Handb Exp Pharmacol. 2009 ; 191: 277-308
34. Hobbs AJ, Moncada S. Antiplatelet properties of a novel, non-NO-based soluble guanylate cyclase activator, BAY 41-2272. Vascul Pharmacol. 2003 ; 40: 149-154
35. Wadelius M, Chen LY, Lindh JD, et al. The largest prospective warfarin-treated cohort supports genetic forecasting. Blood. 2009 ; 113: 784-792