{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:55:40Z","timestamp":1787507740419,"version":"build-2736575974"},"reference-count":66,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2015,3,20]],"date-time":"2015-03-20T00:00:00Z","timestamp":1426809600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Drug Saf"],"published-print":{"date-parts":[[2015,5]]},"DOI":"10.1007\/s40264-015-0275-y","type":"journal-article","created":{"date-parts":[[2015,3,19]],"date-time":"2015-03-19T09:21:53Z","timestamp":1426756913000},"page":"419-435","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Comparative Safety and Tolerability of Endothelin Receptor Antagonists in Pulmonary Arterial Hypertension"],"prefix":"10.1007","volume":"38","author":[{"given":"Meghan","family":"Aversa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Porter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Granton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,3,20]]},"reference":[{"issue":"9","key":"275_CR1","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1164\/rccm.200510-1668OC","volume":"173","author":"M Humbert","year":"2006","unstructured":"Humbert M, Sitbon O, Chaouat A, et al. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med. 2006;173(9):1023\u201330.","journal-title":"Am J Respir Crit Care Med."},{"issue":"1","key":"275_CR2","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1183\/09031936.00092306","volume":"30","author":"AJ Peacock","year":"2007","unstructured":"Peacock AJ, Murphy NF, McMurray JJV, et al. An epidemiological study of pulmonary arterial hypertension. Eur Respir J. 2007;30(1):104\u20139.","journal-title":"Eur Respir J."},{"issue":"18","key":"275_CR3","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1161\/CIRCULATIONAHA.108.847707","volume":"121","author":"SL Archer","year":"2010","unstructured":"Archer SL, Weir EK, Wilkins MR. Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies. Circulation. 2010;121(18):2045\u201366.","journal-title":"Circulation."},{"issue":"25 Suppl","key":"275_CR4","doi-asserted-by":"crossref","first-page":"D34","DOI":"10.1016\/j.jacc.2013.10.029","volume":"62","author":"G Simonneau","year":"2013","unstructured":"Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D34\u201341.","journal-title":"J Am Coll Cardiol."},{"key":"275_CR5","doi-asserted-by":"crossref","first-page":"14S","DOI":"10.1378\/chest.126.1_suppl.14S","volume":"126","author":"M Mcgoon","year":"2004","unstructured":"Mcgoon M, Gutterman D, Steen V, et al. Screening, early detection, and diagnosis of pulmonary arterial hypertension. Chest. 2004;126:14S\u201334S.","journal-title":"Chest."},{"key":"275_CR6","doi-asserted-by":"crossref","first-page":"13S","DOI":"10.1016\/j.jacc.2004.02.029","volume":"43","author":"M Humbert","year":"2004","unstructured":"Humbert M, Morrell NW, Archer SL, et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol. 2004;43:13S\u201324S.","journal-title":"J Am Coll Cardiol."},{"issue":"1","key":"275_CR7","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1177\/107424840200700i102","volume":"7","author":"NHS Kim","year":"2002","unstructured":"Kim NHS, Rubin LJ. Endothelin in health and disease: endothelin receptor antagonists in the management of pulmonary artery hypertension. J Cardiovasc Pharmacol Ther. 2002;7(1):9\u201319.","journal-title":"J Cardiovasc Pharmacol Ther."},{"issue":"1\u20133","key":"275_CR8","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0014-2999(99)00252-6","volume":"375","author":"T Masaki","year":"1999","unstructured":"Masaki T, Miwa S, Sawamura T, et al. Subcellular mechanisms of endothelin action in vascular system. Eur J Pharmacol. 1999;375(1\u20133):133\u20138.","journal-title":"Eur J Pharmacol."},{"key":"275_CR9","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/0006-291X(92)90826-7","volume":"186","author":"M Clozel","year":"1992","unstructured":"Clozel M, Gray GA, Breu V, et al. The endothelin ETB receptor mediates both vasodilation and vasoconstriction in vivo. Biochem Biophys Res Commun. 1992;186:867\u201373.","journal-title":"Biochem Biophys Res Commun."},{"key":"275_CR10","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1378\/chest.129.3.689","volume":"129","author":"D Langleben","year":"2006","unstructured":"Langleben D, Dupuis J, Langleben I, et al. Etiology-specific endothelin-1 clearance in human precapillary pulmonary hypertension. Chest. 2006;129:689\u201393.","journal-title":"Chest."},{"issue":"24","key":"275_CR11","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1056\/NEJM199306173282402","volume":"328","author":"A Giaid","year":"1993","unstructured":"Giaid A, Yanagisawa M, Langleben D, et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med. 1993;328(24):1732\u20139.","journal-title":"N Engl J Med."},{"issue":"6","key":"275_CR12","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1152\/jappl.1995.79.6.2122","volume":"79","author":"SJ Chen","year":"1995","unstructured":"Chen SJ, Chen YF, Meng QC, et al. Endothelin-receptor antagonist bosentan prevents and reverses hypoxic pulmonary hypertension in rats. J Appl Physiol. 1995;79(6):2122\u201331.","journal-title":"J Appl Physiol."},{"key":"275_CR13","first-page":"111","volume":"3","author":"KE Roberts","year":"2009","unstructured":"Roberts KE, Preston IR. Safety and tolerability of bosentan in the management of pulmonary arterial hypertension. Drug Des Devel Ther. 2009;3:111\u20138.","journal-title":"Drug Des Devel Ther."},{"key":"275_CR14","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/S0140-6736(01)06250-X","volume":"358","author":"RN Channick","year":"2001","unstructured":"Channick RN, Simonneau G, Sitbon O, et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet. 2001;358:1119\u201323.","journal-title":"Lancet."},{"key":"275_CR15","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1056\/NEJMoa012212","volume":"346","author":"L Rubin","year":"2002","unstructured":"Rubin L, Badesch D, Barst R, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002;346:896\u2013903.","journal-title":"N Engl J Med."},{"key":"275_CR16","unstructured":"Formulary Journal. Pfizer voluntarily withdraws sitaxsentan from the market worldwide and halts ongoing clinical trials. 2011. http:\/\/formularyjournal.modernmedicine.com\/formulary-journal\/news\/clinical\/clinical-pharmacology\/pfizer-voluntarily-withdraws-sitaxsentan-marke?page=full . Accessed 24 Aug 2014."},{"issue":"6","key":"275_CR17","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1177\/1753465812458014","volume":"6","author":"M D\u2019Alto","year":"2012","unstructured":"D\u2019Alto M. An update on the use of ambrisentan in pulmonary arterial hypertension. Ther Adv Respir Dis. 2012;6(6):331\u201343.","journal-title":"Ther Adv Respir Dis."},{"issue":"1","key":"275_CR18","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s40265-013-0156-6","volume":"74","author":"T Patel","year":"2014","unstructured":"Patel T, McKeage K. Macitentan: first global approval. Drugs. 2014;74(1):127\u201333.","journal-title":"Drugs."},{"issue":"25 Suppl","key":"275_CR19","doi-asserted-by":"crossref","first-page":"D60","DOI":"10.1016\/j.jacc.2013.10.031","volume":"62","author":"N Gali\u00e8","year":"2013","unstructured":"Gali\u00e8 N, Corris PA, Frost A, et al. Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D60\u201372.","journal-title":"J Am Coll Cardiol."},{"issue":"1","key":"275_CR20","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1378\/chest.124.1.247","volume":"124","author":"O Sitbon","year":"2003","unstructured":"Sitbon O, Badesch DB, Channick RN, et al. Effects of the dual endothelin receptor antagonist bosentan in patients with pulmonary arterial hypertension: a 1-year follow-up study. Chest. 2003;124(1):247\u201354.","journal-title":"Chest."},{"key":"275_CR21","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1164\/rccm.200410-1411OC","volume":"171","author":"M Wilkins","year":"2005","unstructured":"Wilkins M, Paul G, Strange J, et al. Sildenafil versus endothelin receptor antagonist for pulmonary hypertension (SERAPH) study. Am J Respir Crit Care Med. 2005;171:1292\u20137.","journal-title":"Am J Respir Crit Care Med."},{"key":"275_CR22","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1111\/j.1365-2141.2010.08097.x","volume":"149","author":"RJ Barst","year":"2010","unstructured":"Barst RJ, Mubarak KK, Machado RF, et al. Exercise capacity and hemodynamics in patients with sickle cell disease and pulmonary hypertension treated with bosentan: results of the ASSET studies. Br J Haematol. 2010;149:426\u201335.","journal-title":"Br J Haematol."},{"issue":"1","key":"275_CR23","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1161\/CIRCULATIONAHA.106.630715","volume":"114","author":"N Gali\u00e8","year":"2006","unstructured":"Gali\u00e8 N, Beghetti M, Gatzoulis M, et al. Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Circulation. 2006;114(1):48\u201354.","journal-title":"Circulation."},{"issue":"1","key":"275_CR24","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ijcard.2007.04.078","volume":"127","author":"M Gatzoulis","year":"2008","unstructured":"Gatzoulis M, Beghetti M, Gali\u00e8 N, et al. Longer-term bosentan therapy improves functional capacity in Eisenmenger syndrome: results of the BREATHE-5 open-label extension study. Int J Cardiol. 2008;127(1):27\u201332.","journal-title":"Int J Cardiol."},{"key":"275_CR25","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1016\/S0140-6736(08)60919-8","volume":"371","author":"N Gali\u00e9","year":"2008","unstructured":"Gali\u00e9 N, Rubin LJ, Hoeper MM, et al. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomized controlled trial. Lancet. 2008;371:2093\u2013100.","journal-title":"Lancet."},{"issue":"2","key":"275_CR26","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.ijcard.2013.12.179","volume":"172","author":"G Simonneau","year":"2014","unstructured":"Simonneau G, Gali\u00e8 N, Jansa P, et al. Long-term results from the EARLY study of bosentan in WHO functional class II pulmonary arterial hypertension patients. Int J Cardiol. 2014;172(2):332\u20139.","journal-title":"Int J Cardiol."},{"issue":"10","key":"275_CR27","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1016\/j.jacc.2006.01.057","volume":"47","author":"RJ Barst","year":"2006","unstructured":"Barst RJ, Langleben D, Badesch D, et al. Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan. J Am Coll Cardiol. 2006;47(10):2049\u201356.","journal-title":"J Am Coll Cardiol."},{"issue":"4","key":"275_CR28","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1378\/chest.07-0767","volume":"134","author":"RL Benza","year":"2008","unstructured":"Benza RL, Barst RJ, Galie N, et al. Sitaxsentan for the treatment of pulmonary arterial hypertension: a 1-year, prospective, open-label observation of outcome and survival. Chest. 2008;134(4):775\u201382.","journal-title":"Chest."},{"key":"275_CR29","doi-asserted-by":"crossref","first-page":"971","DOI":"10.2165\/00002018-200528110-00001","volume":"28","author":"ES Segal","year":"2005","unstructured":"Segal ES, Valette C, Oster L, et al. Risk management strategies in the post-marketing period: safety experience with the US and European bosentan surveillance programmes. Drug Saf. 2005;28:971\u201380.","journal-title":"Drug Saf."},{"issue":"3","key":"275_CR30","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.jacc.2005.04.050","volume":"46","author":"N Gali\u00e9","year":"2005","unstructured":"Gali\u00e9 N, Badesch D, Oudiz R, et al. Ambrisentan therapy for pulmonary arterial hypertension. J Am Coll Cardiol. 2005;46(3):529\u201335.","journal-title":"J Am Coll Cardiol."},{"issue":"23","key":"275_CR31","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1161\/CIRCULATIONAHA.107.742510","volume":"117","author":"N Gali\u00e8","year":"2008","unstructured":"Gali\u00e8 N, Olschewski H, Oudiz RJ, et al. Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation. 2008;117(23):3010\u20139.","journal-title":"Circulation."},{"issue":"21","key":"275_CR32","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1016\/j.jacc.2009.07.033","volume":"54","author":"RJ Oudiz","year":"2009","unstructured":"Oudiz RJ, Gali\u00e8 N, Olschewski H, et al. Long-term ambrisentan therapy for the treatment of pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54(21):1971\u201381.","journal-title":"J Am Coll Cardiol."},{"issue":"1","key":"275_CR33","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.jacc.2012.03.025","volume":"60","author":"O Ben-Yehuda","year":"2012","unstructured":"Ben-Yehuda O, Pizzuti D, Brown A, et al. Long-term hepatic safety of ambrisentan in patients with pulmonary arterial hypertension. J Am Coll Cardiol. 2012;60(1):80\u20131.","journal-title":"J Am Coll Cardiol."},{"key":"275_CR34","unstructured":"GlaxoSmithKline. A post-marketing observational surveillance programme for ambrisentan (VOLT). 2014. http:\/\/www.gsk-clinicalstudyregister.com\/study\/110094#rs . Accessed 24 Aug 2014."},{"issue":"9","key":"275_CR35","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1056\/NEJMoa1213917","volume":"369","author":"T Pulido","year":"2013","unstructured":"Pulido T, Adzerikho I, Channick RN, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369(9):809\u201318.","journal-title":"N Engl J Med."},{"issue":"15","key":"275_CR36","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.2165\/00003088-200443150-00003","volume":"43","author":"J Dingemanse","year":"2004","unstructured":"Dingemanse J, van Giersbergen P. Clinical pharmacology of bosentan, a dual endothelin receptor antagonist. Clin Pharmacokinet. 2004;43(15):1089\u2013115.","journal-title":"Clin Pharmacokinet."},{"issue":"2","key":"275_CR37","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/S0168-8278(02)00107-1","volume":"37","author":"L Fouassier","year":"2002","unstructured":"Fouassier L, Kinnman N, Lef\u00e8vre G, et al. Contribution of mrp2 in alterations of canalicular bile formation by the endothelin antagonist bosentan. J Hepatol. 2002;37(2):184\u201391.","journal-title":"J Hepatol."},{"issue":"4","key":"275_CR38","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1067\/mcp.2001.114667","volume":"69","author":"K Fattinger","year":"2001","unstructured":"Fattinger K, Funk C, Pantze M, et al. The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions. Clin Pharmacol Ther. 2001;69(4):223\u201331.","journal-title":"Clin Pharmacol Ther."},{"issue":"1","key":"275_CR39","doi-asserted-by":"crossref","first-page":"e87548","DOI":"10.1371\/journal.pone.0087548","volume":"9","author":"E Lepist","year":"2014","unstructured":"Lepist E, Gillies H, Smith W, et al. Evaluation of the endothelin receptor antagonists ambrisentan, bosentan, macitentan, and sitaxsentan as hepatobiliary transporter inhibitors and substrates in sandwich-cultured human hepatocytes. PloS One. 2014;9(1):e87548.","journal-title":"PloS One."},{"issue":"2","key":"275_CR40","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1055\/s-0030-1253222","volume":"30","author":"P Lam","year":"2010","unstructured":"Lam P, Soroka C, Boyer J. The bile salt export pump: clinical and experimental aspects of genetic and acquired cholestatic liver disease. Semin Liver Dis. 2010;30(2):125\u201333.","journal-title":"Semin Liver Dis."},{"issue":"13\u201314","key":"275_CR41","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.lfs.2012.02.003","volume":"91","author":"L Ling","year":"2012","unstructured":"Ling L, Kuc RE, Maguire JJ, et al. Comparison of endothelin receptors in normal versus cirrhotic human liver and in the liver from endothelial cell-specific ETB knockout mice. Life Sci. 2012;91(13\u201314):716\u201322.","journal-title":"Life Sci."},{"issue":"2","key":"275_CR42","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1183\/09031936.00138706","volume":"30","author":"M Humbert","year":"2007","unstructured":"Humbert M, Segal ES, Kiely DG, et al. Results of European post-marketing surveillance of bosentan in pulmonary hypertension. Eur Respir J. 2007;30(2):338\u201344.","journal-title":"Eur Respir J."},{"key":"275_CR43","unstructured":"Actelion Pharmaceuticals Inc. Tracleer full prescribing information. 2012. https:\/\/www.tracleer.com\/docs\/Tracleer_Full_Prescribing_Information.pdf . Accessed 24 Aug 2014."},{"issue":"6","key":"275_CR44","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/clpt.2014.42","volume":"95","author":"M Roustit","year":"2014","unstructured":"Roustit M, Fonrose X, Montani D, et al. CYP2C9, SLCO1B1, SLCO1B3, and ABCB11 polymorphisms in patients with bosentan-induced liver toxicity. Clin Pharmacol Ther. 2014;95(6):583\u20135.","journal-title":"Clin Pharmacol Ther."},{"issue":"1","key":"275_CR45","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1177\/0091270002239701","volume":"43","author":"PLM Giersbergen Van","year":"2003","unstructured":"Van Giersbergen PLM, Popescu G, Bodin F, et al. Influence of mild liver impairment on the pharmacokinetics and metabolism of bosentan, a dual endothelin receptor antagonist. J Clin Pharmacol. 2003;43(1):15\u201322.","journal-title":"J Clin Pharmacol."},{"issue":"1","key":"275_CR46","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1183\/09031936.00117511","volume":"41","author":"L Savale","year":"2013","unstructured":"Savale L, Magnier R, Le Pavec J, et al. Efficacy, safety and pharmacokinetics of bosentan in portopulmonary hypertension. Eur Respir J. 2013;41(1):96\u2013103.","journal-title":"Eur Respir J."},{"issue":"3","key":"275_CR47","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1517\/17425255.2011.557181","volume":"7","author":"MS Buckley","year":"2011","unstructured":"Buckley MS, Wicks LM, Staib RL, et al. Pharmacokinetic evaluation of ambrisentan. Expert Opin Drug Metab Toxicol. 2011;7(3):371\u201380.","journal-title":"Expert Opin Drug Metab Toxicol."},{"issue":"1","key":"275_CR48","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1378\/chest.08-1028","volume":"135","author":"MD McGoon","year":"2009","unstructured":"McGoon MD, Frost AE, Oudiz RJ, et al. Ambrisentan therapy in patients with pulmonary arterial hypertension who discontinued bosentan or sitaxsentan due to liver function test abnormalities. Chest. 2009;135(1):122\u20139.","journal-title":"Chest."},{"key":"275_CR49","unstructured":"US Food and Drug Administration. FDA drug safety communication: liver injury warning to be removed from Letairis (ambrisentan) tablets. 2011. http:\/\/www.fda.gov\/Drugs\/DrugSafety\/ucm245852.htm . Accessed 24 Aug 2014."},{"issue":"3","key":"275_CR50","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1177\/1753465814530182","volume":"8","author":"A Steriade","year":"2014","unstructured":"Steriade A, Seferian A, Ja\u00efs X, et al. The potential for macitentan, a new dual endothelin receptor antagonist, in the treatment of pulmonary arterial hypertension. Ther Adv Respir Dis. 2014;8(3):84\u201392.","journal-title":"Ther Adv Respir Dis."},{"issue":"3","key":"275_CR51","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1517\/14740338.2014.859674","volume":"13","author":"J Dingemanse","year":"2014","unstructured":"Dingemanse J, Sidharta PN, Maddrey WC, et al. 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(3):391\u2013405.","journal-title":"Expert Opin Drug Saf."},{"key":"275_CR52","unstructured":"Actelion Pharmaceuticals Inc. Opsumit full prescribing information. 2013. http:\/\/opsumit.com\/sites\/opsumit\/files\/OPSUMIT-Full-Prescribing-Information.pdf . Accessed 24 Aug 2014."},{"issue":"7","key":"275_CR53","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1172\/JCI8609","volume":"105","author":"CE Gariepy","year":"2000","unstructured":"Gariepy CE, Ohuchi T, Williams SC, et al. Salt-sensitive hypertension in endothelin-B receptor\u2013deficient rats. J Clin Invest. 2000;105(7):925\u201333.","journal-title":"J Clin Invest."},{"key":"275_CR54","doi-asserted-by":"crossref","first-page":"F1635","DOI":"10.1152\/ajprenal.90279.2008","volume":"295","author":"Y Ge","year":"2008","unstructured":"Ge Y, Bagnall A, Stricklett PK, et al. Combined knockout of collecting duct endothelin A and B receptors causes hypertension and sodium retention. Am J Physiol Renal Physiol. 2008;295:F1635\u201340.","journal-title":"Am J Physiol Renal Physiol."},{"issue":"2","key":"275_CR55","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1161\/CIRCRESAHA.111.300448","volume":"112","author":"J Nagendran","year":"2013","unstructured":"Nagendran J, Sutendra G, Paterson I, et al. Endothelin axis is upregulated in human and rat right ventricular hypertrophy. Circ Res. 2013;112(2):347\u201354.","journal-title":"Circ Res."},{"issue":"9","key":"275_CR56","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/j.amjcard.2012.06.040","volume":"110","author":"S Shapiro","year":"2012","unstructured":"Shapiro S, Pollock DM, Gillies H, et al. Frequency of edema in patients with pulmonary arterial hypertension receiving ambrisentan. Am J Cardiol. 2012;110(9):1373\u20137.","journal-title":"Am J Cardiol."},{"key":"275_CR57","unstructured":"Gilead Sciences Inc. Letairis full prescribing information. 2014. http:\/\/www.gilead.com\/~\/media\/Files\/pdfs\/medicines\/cardiovascular\/letairis\/letairis_pi . Accessed 24 Aug 2014."},{"issue":"6","key":"275_CR58","first-page":"887","volume":"3","author":"E Gabbay","year":"2007","unstructured":"Gabbay E, Fraser J, McNeil K. Review of bosentan in the management of pulmonary arterial hypertension. Vasc Health Risk Manag. 2007;3(6):887\u2013900.","journal-title":"Vasc Health Risk Manag."},{"key":"275_CR59","unstructured":"Health Canada. Product monograph: Tracleer. Ottawa: Health Canada; 2011 Jun 27."},{"key":"275_CR60","volume-title":"Summary of product characteristics: Tracleer","author":"European Medicines Agency","year":"2012","unstructured":"European Medicines Agency. Summary of product characteristics: Tracleer. London: European Medicines Agency; 2012."},{"key":"275_CR61","unstructured":"European Medicines Agency. Summary of product characteristics: Volibris. London: European Medicines Agency; 2011."},{"key":"275_CR62","unstructured":"Health Canada. Product Monograph: Opsumit. Ottawa: Health Canada; 2013 Nov 1."},{"key":"275_CR63","unstructured":"Health Canada. Product Monograph: Volibris. Ottawa: Health Canada; 2014 Aug 5."},{"key":"275_CR64","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s00228-007-0408-z","volume":"64","author":"G Burgess","year":"2008","unstructured":"Burgess G, Hoogkamer H, Collings L, et al. Mutual pharmacokinetic interactions between steady-state bosentan and sildenafil. Eur J Clin Pharmacol. 2008;64:43\u201350.","journal-title":"Eur J Clin Pharmacol."},{"issue":"12","key":"275_CR65","doi-asserted-by":"crossref","first-page":"4962","DOI":"10.1002\/jps.21789","volume":"98","author":"R Spence","year":"2009","unstructured":"Spence R, Mandagere A, Harrison B, et al. No clinically relevant pharmacokinetic and safety interactions of ambrisentan in combination with tadalafil in healthy volunteers. J Pharm Sci. 2009;98(12):4962\u201374.","journal-title":"J Pharm Sci."},{"key":"275_CR66","first-page":"A4802","volume":"185","author":"PN Sidharta","year":"2012","unstructured":"Sidharta PN, van Giersbergen PLM, Wolzt M, et al. Lack of clinically relevant pharmacokinetic interactions between the dual endothelin receptor antagonist macitentan and sildenafil in healthy subjects [abstract]. Am J Respir Crit Care Med. 2012;185:A4802.","journal-title":"Am J Respir Crit Care Med."}],"container-title":["Drug Safety"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40264-015-0275-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s40264-015-0275-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40264-015-0275-y","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T00:40:32Z","timestamp":1566434432000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s40264-015-0275-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,20]]},"references-count":66,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["275"],"URL":"https:\/\/doi.org\/10.1007\/s40264-015-0275-y","relation":{},"ISSN":["0114-5916","1179-1942"],"issn-type":[{"value":"0114-5916","type":"print"},{"value":"1179-1942","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,20]]}}}