Investigation of the effect of macitentan on the pharmacokinetics and pharmacodynamics of warfarin in healthy male subjects

Clinical Drug Investigation

Volumn 34, Issue 8, 2014, Pages 545-552

  Sidharta, Patricia N ^a   Dietrich, Hartmut ^b   Dingemanse, Jasper ^a  

^a ACTELION PHARMACEUTICALS LTD   (Switzerland)

^b MEDA Manufacturing GmbH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ACT 132577; BLOOD CLOTTING FACTOR 7; DRUG METABOLITE; MACITENTAN; UNCLASSIFIED DRUG; WARFARIN; ANTICOAGULANT AGENT; ENDOTHELIN RECEPTOR ANTAGONIST; PYRIMIDINE DERIVATIVE; SULFONAMIDE;

ADULT; ARTICLE; CONTROLLED STUDY; CROSSOVER PROCEDURE; DRUG BLOOD LEVEL; DRUG SAFETY; DRUG TOLERABILITY; HEADACHE; HUMAN; HUMAN EXPERIMENT; INTERNATIONAL NORMALIZED RATIO; MALE; NORMAL HUMAN; PHARMACODYNAMICS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; ADOLESCENT; CLINICAL TRIAL; MIDDLE AGED; PHASE 1 CLINICAL TRIAL; TREATMENT OUTCOME; YOUNG ADULT;

ADOLESCENT; ADULT; ANTICOAGULANTS; CROSS-OVER STUDIES; ENDOTHELIN RECEPTOR ANTAGONISTS; HUMANS; MALE; MIDDLE AGED; PYRIMIDINES; SULFONAMIDES; TREATMENT OUTCOME; WARFARIN; YOUNG ADULT;

EID: 84904557356     PISSN: 11732563     EISSN: 11791918     Source Type: Journal    
DOI: 10.1007/s40261-014-0207-0     Document Type: Article

References (26)

1. Pulido T, Adzerikho I, Channick RN, Delcroix M, Galie N, Ghofrani HA, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369:809-18.
2. Dingemanse J, Sidharta PN, Maddrey WC, Rubin LJ, Mickail H. Efficacy, safety and clinical pharmacology of macitentan in comparison to other endothelin receptor antagonists in the treatment of pulmonary arterial hypertension. Expert Opin Drug Saf. 2014;13:391-405.
3. Gatfield J, Mueller Grandjean C, Sasse T, Clozel M, Nayler O. Slow receptor dissociation kinetics differentiate macitentan from other endothelin receptor antagonists in pulmonary arterial smooth muscle cells. PLoS One. 2012;7:e47662.
4. Iglarz M, Binkert C, Morrison K, Fischli W, Gatfield J, Treiber A, et al. Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist. J Pharmacol Exp Ther. 2008;327:736-45.
5. Bruderer S, Hopfgartner G, Seiberling M, Wank J, Sidharta PN, Treiber A, et al. Absorption, distribution, metabolism, and excretion of macitentan, a dual endothelin receptor antagonist, in humans. Xenobiotica. 2012;42:901-10.
6. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004;351:1425-36.
7. Kaminsky LS, Zhang ZY. Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73:67-74. (Pubitemid 26425815)
8. Costa IM, Soares PJ, Afonso M, Ratado P, Lanaot JM, Falcao AC. Therapeutic monitoring of warfarin: the appropriate response marker. J Pharm Pharmacol. 2000;52:1405-10.
9. Lippi G, Montagnana M, Salvagno GL, Poli G, Franchini M, Guidi GC. Influence of warfarin therapy on activated factor VII clotting activity. Blood Coagul Fibrinolysis. 2006;17:221-4.
10. Prescribing information: Opsumit® (macitentan) tablets, for oral use. South San Francisco: Actelion Pharmaceuticals US, Inc.; 2013.
11. Sidharta PN, van Giersbergen PL, Dingemanse J. Safety, tolerability, pharmacokinetics, and pharmacodynamics of macitentan, an endothelin receptor antagonist, in an ascending multiple-dose study in healthy subjects. J Clin Pharmacol. 2013;53:1131-8.
12. Kummer O, Haschke M, Hammann F, Bodmer M, Bruderer S, Regnault Y, et al. Comparison of the dissolution and pharmacokinetic profiles of two galenical formulations of the endothelin receptor antagonist macitentan. Eur J Pharm Sci. 2009;38:384-8.
13. Sidharta PN, van Giersbergen PL, Wolzt M, Dingemanse J. Lack of clinically relevant pharmacokinetic interactions between the dual endothelin receptor antagonist macitentan and sildenafil in healthy subjects. Eur Respir J. 2012;(Suppl. 56):165S.
14. Bruderer S, Aanismaa P, Homery MC, Hausler S, Landskroner K, Sidharta PN, et al. Effect of cyclosporine and rifampin on the pharmacokinetics of macitentan, a tissue-targeting dual endothelin receptor antagonist. AAPS J. 2012;14:68-78.
15. Atsmon J, Dingemanse J, Shaikevich D, Volokhov I, Sidharta PN. Investigation of the effects of ketoconazole on the pharmacokinetics of macitentan, a novel dual endothelin receptor antagonist, in healthy subjects. Clin Pharmacokinet. 2013;52:685-92.
16. FDA. Guidance for industry: drug interaction studies - study design, data analysis, implications for dosing and labeling recommendations. Draft guidance. Silver Spring: FDA; 2012.
17. EMA. CPMP/EWP/560/95/Rev. 1 Corr. Guideline on the investigation of drug interactions. London: EMA; 2012.
18. Gu N, Kim BH, Lim KS, Kim SE, Nam WS, Yoon SH, et al. The effect of fimasartan, an angiotensin receptor type 1 blocker, on the pharmacokinetics and pharmacodynamics of warfarin in healthy Korean male volunteers: a one-sequence, two-period crossover clinical trial. Clin Ther. 2012;34:1592-600.
19. Sanwald-Ducray P, Jamois C, Banken L. The effect of aleglitazar on the pharmacokinetics and pharmacodynamics of S- and R-warfarin in healthy male subjects. J Cardiovasc Pharmacol. 2014;63:152-7.
20. Stockis A, van Lier JJ, Cawello W, Kumke T, Eckhardt K. Lack of effect of lacosamide on the pharmacokinetic and pharmacodynamic profiles of warfarin. Epilepsia. 2013;54:1161-6.
21. Yin OQ, Gallagher N, Fischer D, Zhao L, Zhou W, Leroy E, Golor G, Schran H. Effects of nilotinib on single-dose warfarin pharmacokinetics and pharmacodynamics: a randomized, single-blind, two-period crossover study in healthy subjects. Clin Drug Investig. 2011;31:169-79.
22. Braeckman RA, Stirtan WG, Soni PN. Phase 1 study of the effect of icosapent ethyl on warfarin pharmacokinetic and anticoagulation parameters. Clin Drug Investig (Epub 2014 Apr 24).
23. Kreutz R. Pharmacokinetics and pharmacodynamics of rivaroxaban - an oral, direct factor Xa inhibitor. Curr Clin Pharmacol. 2014;9:75-83.
24. Scaglione F. New oral anticoagulants: comparative pharmacology with vitamin K antagonists. Clin Pharmacokinet. 2013;52:69-82.
25. Bauer KA. Recent progress in anticoagulant therapy: oral direct inhibitors of thrombin and factor Xa. J Thromb Haemost. 2011;9(Suppl 1):12-9.
26. Mueck W, Schwers S, Stampfuss J. Rivaroxaban and other novel oral anticoagulants: pharmacokinetics in healthy subjects, specific patient populations and relevance of coagulation monitoring. Thromb J. 2013;11:10.