The new endothelin receptor antagonist macitentan: Prospects for therapy of pulmonary arterial hypertension
- 作者: Avdeev SN1
-
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- 期: 卷 88, 编号 7 (2016)
- 页面: 89-97
- 栏目: Editorial
- ##submission.dateSubmitted##: 10.04.2020
- ##submission.datePublished##: 15.07.2016
- URL: https://ter-arkhiv.ru/0040-3660/article/view/32026
- ID: 32026
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Pulmonary arterial hypertension (PAH) is a clinical group of severe and rare diseases with similar morphological, hemodynamic, and therapeutic characteristics. One of the novel drugs to treat PAH is macitentan, a new double endothelin ETA and ETB receptor antagonist that is characterized by special physicochemical properties, ensuring the penetration of the drug into tissues and its improved receptor-binding properties. The SERAPHIN trial has demonstrated that therapy with macitentan 10 mg versus placebo statistically significantly reduces the risk of poor outcomes and death by 45%. The treatment with macitentan 10 is observed to be highly effective regardless of the presence/absence of basic PAH-specific therapy. The drug considerably improves clinically important outcomes, including 6-minute walk distance and WHO functional class. Macitentan exerts a steady-state therapeutic effect, by improving pulmonary hemodynamics. Macitentan 10 mg statistically significantly reduces the risk of PAH, frequency of its related hospitalizations, and the number of days spent in hospital. The drug has a favorable safety profile; its most common side effects are headache, nasopharyngitis, and anemia. Macitentan is an effective first-line drug to improve long-term outcomes in patients with newly and previously diagnosed PAH.
参考
- Galiè N, Humbert M, Vachiery J-L, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Noordegraaf AV, Beghetti M, Ghofrani A, Sanchez MAG, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). Eur Respir J. 2016;37:67-119. doi: 10.1183/13993003.51032-2015
- Чазова И.Е., Мартынюк Т.В., Авдеев С.Н., Волков А.В., Наконечников С.Н. Клинические рекомендации по диагностике и лечению легочной гипертензии. Евразийский кардиологический журнал. 2014;4:4-24.
- Hoeper M.M., Bogaard H.J., Condliffe R., Fratz R., Khanna D., Kurzuna M, Langleben D, Manes A, Satoh T, Torres F, Wilkins MR, Badesch DB. Definitions and Diagnosis of Pulmonary Hypertension. J Am Coll Cardiol. 2013;62 (25Suppl.):D42-50. doi: 10.1016/j.jacc.2013.10.032
- D’Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT, Levy PS, Pietra GG, Reid LM, Reeves JT, Rich S, Vreim CE, Williams GW, Wu M. Survival in patients with primary pulmonary hypertension: Results from a national prospective registry. Ann Intern Med. 1991;115:343-349. doi: 10.7326/0003-4819-115-5-343
- Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, Yaïci A, Weitzenblum E, Cordier J-F, Chabot F, Dromer C, Pison C, Reynaud-Gaubert M, Haloun A, Laurent M, Hachulla E, Cottin V, Degano B, Jaïs X, Montani D, Souza R, Simonneau G. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation. 2010;122:156-163. doi: 10.1161/CIRCULATIONAHA.109.911818
- Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, Sanchez MAJ, Kumar RK, Landzberg M, Machado RF, Olschewski H, Robbins IM, Souza R. Updated Clinical Classification of Pulmonary Hypertension. J Am Coll Cardiol. 2013;25(Suppl.):34-41. doi: 10.1016/j.jacc.2013.10.029
- Morrell NW, Adnot S, Archer SL, Dupuis J, Jones PL, MacLean MR, McMurtry IF, Stenmark KR, Thistlethwaite PA, Weissmann N, Yuan JXJ, Weir EK. Cellular and molecular basis of pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54:S20-S31. doi: 10.1016/j.jacc.2009.04.018
- Hassoun PM, Mouthon L, Barbera JA, Eddahibi S, Flores SC, Grimminger F, Jones PL, Maitland ML, Michelakis ED, Morell NW, Newman JH, Rabinovitch M, Schermuly R, Stenmark KR, Voelkel NF, Yuan JX-J, Humbert M. Inflammation, growth factors, and pulmonary vascular remodeling. J Am Coll Cardiol. 2009;54:S10-S19. doi: 10.1016/j.jacc.2009.04.006
- McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J. 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, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009;53:1573-1619. doi: 10.1161/CIRCULATIONAHA.109.192230
- Barst RJ, Gibbs JSR, Ghofrani HA, Hoeper MM, McLaughlin VV, Rubin LJ, Sitbon O, Tapson VF, Galiè N. Updated evidence-based treatment algorithm in pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54:S78-84. doi: 10.1016/j.jacc.2009.04.017
- Sitbon O, Humbert M, Jaïs X, Ioos V, Hamid AM, Provencher S, Garcia G, Parent F, Hervé P, Simonneau G. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation. 2005;111:3105-3111. doi: 10.1161/CIRCULATIONAHA.104.488486
- Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004;351:1425-1436. doi: 10.1056/NEJMra040291
- Ortega Mateo A, de Artiñano AA. Highlights on endothelins: a review. Pharmacol Res. 1997;36:339-351. doi: 10.1006/phrs.1997.0246
- Raja SG. Review: Endothelin receptor antagonists for pulmonary arterial hypertension: an overview. Cardiovasc Ther. 2010;28:e65-71. doi: 10.1111/j.1755-5922.2010.00158.x
- Berti F, Rossoni G, Delia D, Villa LM, Buschi A, Trento F, Berti M, Tondo C. Nitric oxide and prostacyclin influence coronary vasomotor tone in perfused rabbit heart and modulate endothelin-1 activity. J Cardiovasc Pharmacol. 1993;22:321-326. doi: 10.1097/00005344-199308000-00023
- Pollock DM, Boesen EI, Black SM. Does targeting the lipophilic milieu provide advantages for an endothelin antagonist? Mol Interv. 2009;9:75-78. doi: 10.1124/mi.9.2.6
- Giaid A, Yanagisawa M, Langleben D, Michel RP, Levy R, Shennib H, Kimura S, Masaki T, Duguid WP, Stewart DJ. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med. 1993;328:1732-1739. doi: 10.1056/NEJM199306173282402
- Dupuis J, Hoeper MM. Endothelin receptor antagonists in pulmonary arterial hypertension. Eur Respir J. 2008;31:407-415. doi: 10.1183/09031936.00078207
- Hirata Y, Emori T, Eguchi S, Kanno K, Imai T, Ohta K, Marumo F. Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells. J Clin Invest. 1993;91:1367-1373. doi: 10.1172/jci116338
- Shi-Wen X, Chen Y, Denton CP, Eastwood M, Renzoni EA, Bou-Gharios G, Pearson JD, Dashwood M, du Bois RM, Black CM, Leask A, Abraham DJ. Endothelin-1 promotes myofibroblast induction through the ETA receptor via a rac/phosphoinositide 3-kinase/Akt-dependent pathway and is essential for the enhanced contractile phenotype of fibrotic fibroblasts. Mol Biol Cell. 2004;15:2707-2719. doi: 10.1091/mbc.E03-12-0902
- Bolli MH, Boss C, Binkert C, Buchmann S, Bur D, Hess P, Iglars M, Meyer S, Rein J, Rey M, Treiber A, Clozel M, Fischli W, Weller T. The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl) oxy]ethoxy]-4-pyrimidinyl]-N’-propylsulfamide (Macitentan), an orally active, potent dual endothelin receptor antagonist. J Med Chem. 2012;55:7849-7861. doi: 10.1021/jm3009103
- Iglarz M, Binkert C, Morrison K, Fischli W, Gatfield J, Treiber A, Weller T, Bolli MH, Boss C, Buchmann S, Capeleto B, Hess P, Qiu C, Clozel M. Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist. J Pharmacol Exp Ther. 2008;327:736-745. doi: 10.1124/jpet.108.142976
- Gatfield J, Grandjean CM, 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. doi: 10.1371/journal.pone.0047662
- Bruderer S, Aänismaa P, Homery M-C, Häusler S, Landskroner K, Sidharta PN, Treiber A, Dingemanse J. Effect of cyclosporine and rifampin on the pharmacokinetics of macitentan, a tissue-targeting dual endothelin receptor antagonist. AAPS J. 2012;14: 68-78. doi: 10.1208/s12248-011-9316-3
- Sidharta PN, van Giersbergen PLM, Halabi A, Dingemanse J. Macitentan: entry-into humans study with a new endothelin receptor antagonist. Eur J Clin Pharmacol. 2011;67:977-984. doi: 10.1007/s00228-011-1043-2
- Sidharta PN, van Giersbergen PLM, 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;53:1131-1138. doi: 10.1002/jcph.152
- Pulido T, Adzerikho I, Channick R, Delcroix M, Galiè N, Ghofrani H-A, Jansa P, Jing Z-C, Brun F-O, Mehta S, Mittelholzer CM, Perchenet L, Sitbon O, Souza R, Torbicki A, Zeng X, Rubin LJ, Simonneau G. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369:809-818. doi: 10.1056/NEJMoa1213917
- Channick RN, Delcroix M, Ghofrani H-A, Hunsche E, Jansa P, Le Brun F-O, Mehta S, Pulido T, Rubin LJ, Sastry BKS, Simonneau G, Sitbon O, Souza R, Torbicki A, Galiè N. Effect of macitentan on hospitalizations: results from the SERAPHIN trial. JACC Heart Fail. 2015;3:1-8. doi: 10.1016/j.jchf.2014.07.013
- Simonneau G, Channick RN, Delcroix M, Galiè N, Ghofrani H-A, Jansa P, Le Brun F-O, Mehta S, Perchenet L, Pulido T, Sastry BKS, Sitbon O, Souza R, Torbicki A, Rubin LJ. Incident and prevalent cohorts with pulmonary arterial hypertension: insight from SERAPHIN. Eur Respir J. 2015;46:1711-1720. doi: 10.1183/13993003.00364-2015