{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T14:59:20Z","timestamp":1715957960190},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,12,29]],"date-time":"2015-12-29T00:00:00Z","timestamp":1451347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Actelion Pharmaceuticals Ltd, Allschwil, Switzerland"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Macitentan, a dual endothelin receptor antagonist used in pulmonary arterial hypertension, induces cytochrome P450 (CYP) 3A at supratherapeutic concentrations in vitro. Most combined oral hormonal contraceptives (OCs) are CYP3A substrates and their efficacy can be affected by CYP3A inducers. This randomized crossover study assessed possible pharmacokinetic (PK) interactions between macitentan and an OC containing ethinyl estradiol and norethindrone (or norethisterone). Twenty\u2010six healthy women received a single oral dose of OC alone (reference) and concomitantly with 10 mg macitentan at steady state (test). No PK interaction was concluded if the 90% confidence intervals (CIs) of geometric mean ratios (GMRs; test\/reference) of the peak plasma concentration (C<jats:sub>max<\/jats:sub>) and the exposure from 0 to infinity (AUC<jats:sub>0<\/jats:sub><jats:italic><jats:sub>\u2013<\/jats:sub><\/jats:italic><jats:sub>\u221e<\/jats:sub>) to the OC components were within the equivalence limits of 0.8 to 1.25. C<jats:sub>max<\/jats:sub> and AUC<jats:sub>0\u2013\u221e<\/jats:sub> of the OC were within the equivalence limits. For ethinyl estradiol, GMRs (90%CIs) of C<jats:sub>max<\/jats:sub> and AUC<jats:sub>0\u2013\u221e<\/jats:sub> were 0.92 (0.85\u20130.99) and 0.95 (0.90\u20130.99). For norethindrone, these values were 1.02 (0.95\u20131.09) and 1.04 (0.98\u20131.09), respectively. Overall, study treatments were well tolerated. No major changes from baseline in safety parameters were reported in either treatment. Macitentan does not affect the PK of OCs.<\/jats:p>","DOI":"10.1002\/jcph.639","type":"journal-article","created":{"date-parts":[[2015,9,18]],"date-time":"2015-09-18T07:06:47Z","timestamp":1442560007000},"page":"669-674","source":"Crossref","is-referenced-by-count":8,"title":["Lack of Pharmacokinetic Interactions Between Macitentan and a Combined Oral Contraceptive in Healthy Female Subjects"],"prefix":"10.1002","volume":"56","author":[{"given":"No\u00e9mie","family":"Hurst","sequence":"first","affiliation":[{"name":"Actelion Pharmaceuticals Ltd Department of Clinical Pharmacology  Allschwil Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Pellek","sequence":"additional","affiliation":[{"name":"ClinPharmCologne MEDA  K\u00f6ln Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasper","family":"Dingemanse","sequence":"additional","affiliation":[{"name":"Actelion Pharmaceuticals Ltd Department of Clinical Pharmacology  Allschwil Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia N.","family":"Sidharta","sequence":"additional","affiliation":[{"name":"Actelion Pharmaceuticals Ltd Department of Clinical Pharmacology  Allschwil Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,12,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.23.1.f192"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890310017477"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/rr44"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.02.029"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm3009103"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047662"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0107809"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.142976"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1213917"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2014.07.013"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199701093360207"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.09-1140"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.10.029"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/709407"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1783\/147118906776276486"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehp297"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(98)00162-4"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920008786485137"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0890-6238(98)00064-1"},{"issue":"6","key":"e_1_2_8_21_1","first-page":"26","article-title":"Oral contraceptive therapy in women: drug interactions and unwanted outcomes","volume":"2","author":"Schwartz JB.","year":"1999","journal-title":"J Gend Specif Med"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199937060-00004"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.5414\/CPP44113"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7742(08)00006-8"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/009127009803801109"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2003.08.009"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498254.2012.664665"},{"key":"e_1_2_8_28_1","unstructured":"Summary of Product Characteristics: Opsumit\u00ae (macitentan) 10 mg tablets fou. 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