{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:50:00Z","timestamp":1790517000334,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,6,5]],"date-time":"2018-06-05T00:00:00Z","timestamp":1528156800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2018,8]]},"abstract":"Abstract<\/jats:title>The approval of macitentan has increased the number of pharmacological treatments of pulmonary arterial hypertension (PAH<\/jats:styled-content>). Here, we review the effect on PAH<\/jats:styled-content> of macitentan compared to other endothelin receptor antagonists. Drugs targeting the endothelin (ET<\/jats:styled-content>) pathway include the selective ETA<\/jats:sub><\/jats:styled-content> receptor antagonist ambrisentan, the ETA<\/jats:sub><\/jats:styled-content>\/ETB<\/jats:sub><\/jats:styled-content> receptor antagonists, bosentan and macitentan, which were recently approved for PAH<\/jats:styled-content> treatment. Macitentan exhibits higher antagonistic potency than bosentan and ambrisentan in pulmonary smooth muscle cells. Compared to ambrisentan and bosentan, macitentan has a longer duration of action, reflected by the longer half\u2010life, as well as pharmacodynamics attributed to its active metabolite, ACT<\/jats:styled-content>\u2010132577. The efficacy of macitentan on PAH<\/jats:styled-content> was investigated in the phase III <\/jats:styled-content>SERAPHIN<\/jats:styled-content><\/jats:italic> trial (NCT<\/jats:styled-content>00660179). Macitentan significantly reduced morbidity and mortality. It improved the 6\u2010min. walk distance (6MWD<\/jats:styled-content>) among PAH<\/jats:styled-content> patients. In the AMB<\/jats:styled-content>\u2010320\/321\u2010E<\/jats:italic> (NCT<\/jats:styled-content>00578786) study, ambrisentan improved exercise capacity. In the EARLY<\/jats:styled-content><\/jats:italic> study (NCT<\/jats:styled-content>00091715), bosentan showed improvements in 6MWD<\/jats:styled-content> which were not statistically significant. Bosentan had an effect on PAH<\/jats:styled-content> in patients with Eisenmenger syndrome (ES<\/jats:styled-content>) in the BREATHE<\/jats:styled-content>\u20105<\/jats:italic> study (NCT<\/jats:styled-content>00367770), while macitentan did not improve 6MWD<\/jats:styled-content> in these patients, but there are differences regarding study size and functional class, and that 30% of the patients treated with macitentan were already in treatment with a phosphodiesterase type 5 inhibitor. Macitentan revealed a lower risk of developing peripheral oedema and hepatotoxicity in the SERAPHIN<\/jats:styled-content><\/jats:italic> study. In summary, macitentan has an efficiency comparable to bosentan and ambrisentan in the treatment of PAH<\/jats:styled-content>. Patients treated with macitentan exhibited less adverse effects compared to bosentan and ambrisentan. In patients with PAH<\/jats:styled-content> associated with ES<\/jats:styled-content>, the trials with bosentan and macitentan do not seem comparable, and it needs to be clarified whether these drugs are effective when administered as part of a combination treatment in this condition.<\/jats:p>","DOI":"10.1111\/bcpt.13033","type":"journal-article","created":{"date-parts":[[2018,5,2]],"date-time":"2018-05-02T19:19:40Z","timestamp":1525288780000},"page":"103-113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["A Focus on Macitentan in the Treatment of Pulmonary Arterial Hypertension"],"prefix":"10.1111","volume":"123","author":[{"given":"Martin","family":"Bedan","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Pharmacology Aarhus University Aarhus C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Grimm","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Pharmacology Aarhus University Aarhus C Denmark"},{"name":"Clinic for Plastic, Aesthetic and Hand Surgery Otto\u2010von\u2010Guericke\u2010University Magdeburg Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Wehland","sequence":"additional","affiliation":[{"name":"Clinic for Plastic, Aesthetic and Hand Surgery Otto\u2010von\u2010Guericke\u2010University Magdeburg Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Simonsen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Pharmacology Aarhus University Aarhus C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Infanger","sequence":"additional","affiliation":[{"name":"Clinic for Plastic, Aesthetic and Hand Surgery Otto\u2010von\u2010Guericke\u2010University Magdeburg Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Clinic for Plastic, Aesthetic and Hand Surgery Otto\u2010von\u2010Guericke\u2010University Magdeburg Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,5]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.9739.1"},{"key":"e_1_2_15_3_1","unstructured":"Pulmonal hypertension \u2013 Dansk Cardiologisk Selskab. Available from:www.cardio.dk\/docman\/doc_download\/139-pulmonal-hypertension(August 2005; last accessed on 20 August 17)."},{"key":"e_1_2_15_4_1","unstructured":"Pulmonal hypertension.http:\/\/nbv.cardio.dk\/pah#afs13_2(5.6.17; last accessed on 20 August 2017)."},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-013-0156-6"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.301146"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047662"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.7326\/M14-2385"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv317"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-8-97"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00021915"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.4103\/2045-8932.94843"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2013.09.002"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.10.002"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5223(95)70415-9"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(85)90241-1"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9150(89)90022-1"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1592"},{"key":"e_1_2_15_19_1","first-page":"265","article-title":"Epoprostenol sodium for treatment of pulmonary arterial hypertension","volume":"11","author":"Saito Y","year":"2015","journal-title":"Vasc Health Risk Manag"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-662-45805-1_8"},{"key":"e_1_2_15_21_1","first-page":"382","article-title":"Role of prostacyclin in pulmonary hypertension","volume":"2014","author":"Mitchell JA","year":"2014","journal-title":"Glob Cardiol Sci Pract"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.2217\/fca.13.6"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.4103\/0976-500X.149151"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1586\/17476348.2014.937708"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0255-5"},{"key":"e_1_2_15_26_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20100145"},{"key":"e_1_2_15_27_1","volume-title":"Integrated Systems Physiology: From Molecule to Function. Regulation of Vascular Smooth Muscle Function","author":"Khalil RA","year":"2010"},{"key":"e_1_2_15_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00748.2004"},{"key":"e_1_2_15_29_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.165.3.2104059"},{"key":"e_1_2_15_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.fjc.0000175877.25296.bd"},{"key":"e_1_2_15_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2009.01.006"},{"key":"e_1_2_15_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116338"},{"key":"e_1_2_15_33_1","doi-asserted-by":"publisher","DOI":"10.1183\/09059180.00004812"},{"key":"e_1_2_15_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/15.6.758"},{"key":"e_1_2_15_35_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.115.011833"},{"key":"e_1_2_15_36_1","unstructured":"Pubchem Macitentan.https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Macitentan#section=Top[11.11.2017; cited]."},{"key":"e_1_2_15_37_1","first-page":"665","article-title":"Macitentan for the treatment of pulmonary arterial hypertension","volume":"10","author":"Kholdani CA","year":"2014","journal-title":"Vasc Health Risk Manag"},{"key":"e_1_2_15_38_1","unstructured":"Drug information. Macitentan EMA approval date.http:\/\/www.phaeurope.org\/news-and-research\/drug-information\/(2.2.15; last accessed on 8 November 2017)."},{"key":"e_1_2_15_39_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.107.119206"},{"key":"e_1_2_15_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2009.02.016"},{"key":"e_1_2_15_41_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2015.1000859"},{"key":"e_1_2_15_42_1","doi-asserted-by":"publisher","DOI":"10.1586\/17512433.2014.919849"},{"key":"e_1_2_15_43_1","unstructured":"Pregnancy categories.https:\/\/www.fda.gov\/ohrms\/dockets\/ac\/02\/slides\/3902s1-09-miller\/tsld009.htm(last accessed on 3 November 2018)."},{"key":"e_1_2_15_44_1","unstructured":"European Commission.Summary of product characteristics.https:\/\/ec.europa.eu\/health\/documents\/community-register\/2013\/20131220127396\/anx_127396_en.pdf(2013; last accessed on 17 November 2017)."},{"key":"e_1_2_15_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1213917"},{"key":"e_1_2_15_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60919-8"},{"key":"e_1_2_15_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.07.033"},{"key":"e_1_2_15_48_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201203-0480OC"},{"key":"e_1_2_15_49_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.630715"},{"key":"e_1_2_15_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx493.P5462"},{"key":"e_1_2_15_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40256-017-0260-1"},{"key":"e_1_2_15_52_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2001.114667"},{"key":"e_1_2_15_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12856"},{"key":"e_1_2_15_54_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00475.2015"},{"key":"e_1_2_15_55_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.003896"},{"key":"e_1_2_15_56_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270011423662"},{"key":"e_1_2_15_57_1","unstructured":"Ambrisentan chemical structure.https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Ambrisentan#section=Top(1.13.2018; last accessed on 29 January 2018)."},{"key":"e_1_2_15_58_1","unstructured":"Bosentan chemical structure.https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Bosentan#section=Top(1.13.2018; last accessed on 29 January 2018)."},{"key":"e_1_2_15_59_1","unstructured":"Macitentan.https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Macitentan#section=Top(11.11.2017; last accessed on 15 November 2017)."},{"key":"e_1_2_15_60_1","unstructured":"ACT\u2010132577.https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/25099191#section=Top(11.11.2017; last accessed on 15 November 2017)."},{"key":"e_1_2_15_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-662-45805-1_9"},{"key":"e_1_2_15_62_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200443150-00003"},{"key":"e_1_2_15_63_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2011.557181"},{"key":"e_1_2_15_64_1","volume-title":"Kompendium i farmakologi","author":"Steen AMF","year":"2015"},{"key":"e_1_2_15_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(17)30305-3"},{"key":"e_1_2_15_66_1","unstructured":"Actelion initiates phase III study to evaluate macitentan (Opsumit) in children with PAH.https:\/\/www1.actelion.com\/investors\/news-archive?newsId=2025902(8.14.2017; last accessed on 17 November 2017)."}],"container-title":["Basic & Clinical Pharmacology & Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcpt.13033","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.13033","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T05:16:56Z","timestamp":1695014216000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bcpt.13033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,5]]},"references-count":65,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,8]]}},"alternative-id":["10.1111\/bcpt.13033"],"URL":"https:\/\/doi.org\/10.1111\/bcpt.13033","archive":["Portico"],"relation":{},"ISSN":["1742-7835","1742-7843"],"issn-type":[{"value":"1742-7835","type":"print"},{"value":"1742-7843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,5]]},"assertion":[{"value":"2018-02-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}