{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T15:24:59Z","timestamp":1774538699753,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Pulm. circ."],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:p>Female patients requiring treatment for pulmonary arterial hypertension (PAH) are advised to avoid pregnancy because of the high associated mortality rate. Oral contraception is one of the main methods of preventing pregnancy in this context, mandating pharmacokinetic and safety studies for new agents in this setting. Riociguat is a soluble guanylate cyclase stimulator approved for treatment of PAH and inoperable and persistent or recurrent chronic thromboembolic pulmonary hypertension. This single\u2010center, randomized, nonblinded study involving healthy postmenopausal women investigated the effect of riociguat on plasma concentrations of levonorgestrel (0.15\u00a0mg) and ethinylestradiol (0.03\u00a0mg) in a combined oral contraceptive. Treatment A was a single oral tablet of levonorgestrel\u2010ethinylestradiol. In treatment B, subjects received 2.5\u00a0mg riociguat 3 times daily for 12\u00a0days. On the eighth day, they also received a single oral tablet of levonorgestrel\u2010ethinylestradiol. Subjects received both regimens in a crossover design. There was no change in area under the plasma concentration\u2014time curves of levonorgestrel or ethinylestradiol or maximum concentration in plasma (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) of levonorgestrel during combined administration versus levonorgestrel\u2010ethinylestradiol alone. A 20% increase in the <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> of ethinylestradiol was noted during coadministration; this is not anticipated to adversely impact the contraceptive efficacy or to require any dose adjustment for ethinylestradiol. Plasma concentrations and exposures of riociguat were within the expected range and were not influenced by coadministration with levonorgestrel\u2010ethinylestradiol. Combined treatment was safe and well tolerated. In conclusion, riociguat did not change the exposure to levonorgestrel or ethinylestradiol relative to oral contraceptive administered alone.<\/jats:p>","DOI":"10.1086\/685428","type":"journal-article","created":{"date-parts":[[2016,3,11]],"date-time":"2016-03-11T14:29:50Z","timestamp":1457706590000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Pharmacokinetic Interaction Study between Riociguat and the Combined Oral Contraceptives Levonorgestrel and Ethinylestradiol in Healthy Postmenopausal Women"],"prefix":"10.1002","volume":"6","author":[{"given":"Reiner","family":"Frey","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Pharma Research Center Bayer Pharma Wuppertal Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sigrun","family":"Unger","sequence":"additional","affiliation":[{"name":"Global Biostatistics Pharma Research Center Bayer Pharma Wuppertal Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorina","family":"van der Mey","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Pharma Research Center Bayer Pharma Wuppertal Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corina","family":"Becker","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Pharma Research Center Bayer Pharma Wuppertal Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soundos","family":"Saleh","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Pharma Research Center Bayer Pharma Wuppertal Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Wensing","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Pharma Research Center Bayer Pharma Wuppertal Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"M\u00fcck","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Pharma Research Center Bayer Pharma Wuppertal Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01032-2015"},{"key":"e_1_2_8_3_1","unstructured":"Bayer HealthCare Pharmaceuticals.Prescribing information [Adempas (riociguat) tablets]. Accessed June 27 2014.http:\/\/labeling.bayerhealthcare.com\/html\/products\/pi\/Adempas_PI.pdf."},{"key":"e_1_2_8_4_1","unstructured":"European Medicines Agency.Annex I: summary of product characteristics [Adempas (riociguat tablets)]. Published March 27 2014. Accessed November 25 2014.http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/EPAR_\u2010_Product_Information\/human\/002737\/WC500165034.pdf."},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1209655"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1209657"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-68964-5_13"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.981738"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-662-45805-1_12"},{"key":"e_1_2_8_10_1","unstructured":"Bayer Pharma.Yasmin prescribing information. Revised May2015.http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2015\/021098s023lbl.pdf."},{"key":"e_1_2_8_11_1","unstructured":"Pfizer. Revatio: US prescribing information. Revised March2014.http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2014\/021845s011 022473s004 0203109s002lbl.pdf."},{"key":"e_1_2_8_12_1","unstructured":"Eli Lilly. Adcirca prescribing information. Revised April2015.http:\/\/www.drugs.com\/pro\/adcirca.html."},{"key":"e_1_2_8_13_1","unstructured":"Actelion. Tracleer: highlights of prescribing information. Revised December2015.https:\/\/www.tracleer.com\/docs\/Tracleer_Full_Prescribing_Information.pdf."},{"key":"e_1_2_8_14_1","article-title":"Lack of pharmacokinetic interactions between macitentan and a combined oral contraceptive in healthy female subjects","author":"Hurst N","journal-title":"J Clin Pharmacol."},{"key":"e_1_2_8_15_1","unstructured":"Bayer PLC. Microgynon [summary of product characteristics]. Updated July 6 2015.https:\/\/www.medicines.org.uk\/emc\/medicine\/1827."},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/2050-6511-14-S1-P5"}],"container-title":["Pulmonary Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1086\/685428","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1086\/685428","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1086\/685428","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T12:32:04Z","timestamp":1693225924000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1086\/685428"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3]]},"references-count":15,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["10.1086\/685428"],"URL":"https:\/\/doi.org\/10.1086\/685428","archive":["Portico"],"relation":{},"ISSN":["2045-8940","2045-8940"],"issn-type":[{"value":"2045-8940","type":"print"},{"value":"2045-8940","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3]]}}}