{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T12:11:30Z","timestamp":1779970290817,"version":"3.53.1"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004331","name":"Johnson and Johnson","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004331","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Macitentan is an oral, dual ET\n                    <jats:sub>A<\/jats:sub>\n                    \/ET\n                    <jats:sub>B<\/jats:sub>\n                    endothelin receptor antagonist, currently approved in adults for the treatment of pulmonary arterial hypertension (PAH) at a once\u2010daily dose of 10 mg. Pre\u2010clinical and clinical data suggest that greater ET\n                    <jats:sub>B<\/jats:sub>\n                    receptor inhibition may result in greater efficacy. This hypothesis is being tested in the Phase 3 UNISUS study (NCT04273945), comparing once\u2010daily macitentan 75 mg versus macitentan 10 mg.\n                  <\/jats:p>\n                  <jats:p>The present Phase 1 study (NCT04211272) evaluated the pharmacokinetics and safety of concomitant administration of once\u2010daily macitentan 75 mg at steady state with substrates of either breast cancer resistance protein (BCRP) transporter (e.g., riociguat and rosuvastatin) or cytochrome P450 3A4 (CYP3A4) enzymes (e.g., sildenafil and tadalafil) in healthy male adults. Macitentan was administered once daily at 10 mg on Days 1 and 2, 37.5 mg on Days 3\u20105, and 75 mg on Days 6\u201013. Participants received a single oral dose of sildenafil (20 mg) on Days \u22124 and 13, riociguat (1 mg) on Days \u22123 and 10, or rosuvastatin (10 mg) on Days \u22124 and 10.<\/jats:p>\n                  <jats:p>Geometric mean ratios for the maximum concentration and area under the curve of the substrate and 90% confidence intervals showed no clinically relevant effects on exposure for sildenafil, riociguat, or rosuvastatin when administered alone or with macitentan 75 mg. Co\u2010administration of macitentan and the substrates was generally well tolerated. Due to the lack of clinically relevant drug\u2013drug pharmacokinetic interactions, no dose adjustment is deemed necessary when co\u2010administering once\u2010daily macitentan 75 mg with BCRP or CYP3A4 substrates.<\/jats:p>","DOI":"10.1002\/jcph.70185","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T14:14:19Z","timestamp":1776953659000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Once\u2010Daily Macitentan 75 mg on the Pharmacokinetics of Sildenafil, Riociguat, or Rosuvastatin in Healthy Male Participants"],"prefix":"10.1002","volume":"66","author":[{"given":"D\u00e9nes","family":"Csonka","sequence":"first","affiliation":[{"name":"Johnson &amp; Johnson  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Gargano","sequence":"additional","affiliation":[{"name":"Johnson and Johnson  Spring House PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navin","family":"Goyal","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Raritan NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"De Meulder","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitaly","family":"Yartsev","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Jose Perez","family":"Ruixo","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac237"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20102600(24)00295\u20109"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.122.029024"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010025\u201002287\u20108"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20102600(24)00425\u20109"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2020.08.2069"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202009\u20103698OC"},{"key":"e_1_2_11_9_1","unstructured":"NHS Digital.National Audit of PH 15th Annual Report. 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