{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T10:14:09Z","timestamp":1760523249797},"reference-count":27,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Faldaprevir is a potent hepatitis C virus (HCV) NS3\/4A protease inhibitor. Faldaprevir is known to inhibit P-glycoprotein, CYP3A4, and UDP-glucuronosyltransferase 1A1. This study evaluated the effect of steady-state 240 mg faldaprevir on the pharmacokinetics (PK) of an oral contraceptive containing ethinylestradiol (EE) and levonorgestrel (LNG) in healthy premenopausal women. In period 1, subjects received EE\/LNG once daily (QD) for 14 days. Blood samples were taken on days 1, 11, and 12, with intensive PK blood sampling for EE and LNG on day 13. In period 2, subjects received EE-LNG QD and 240 mg faldaprevir QD on days 14 to 21 (240 mg faldaprevir twice daily on day 14). Blood samples were taken on days 14, 19, and 20, with PK profiling samples obtained for EE and LNG on day 21. A total of 15\/16 subjects completed the study. Overall, EE and LNG exposure (assessed by the area under the curve) was approximately 1.4-fold higher when EE and LNG were coadministered with faldaprevir than when administered alone. Median\n            <jats:italic>t<\/jats:italic>\n            <jats:sub>1\/2<\/jats:sub>\n            (terminal half-life in plasma at steady state) values were prolonged for both EE (2.4 h longer) and LNG (4.7 h longer) when EE and LNG were coadministered with faldaprevir. The mean oral clearance and apparent volume of distribution of both EE and LNG were lower (\u223c30%) when EE and LNG were coadministered with faldaprevir. Coadministration of faldaprevir and an oral contraceptive resulted in a moderate increase in exposure to both EE and LNG. However, this increase was not considered clinically meaningful, and no dose adjustment of oral contraceptives was deemed necessary. (This study has been registered at ClinicalTrials.gov under registration number NCT01570244.)\n          <\/jats:p>","DOI":"10.1128\/aac.03589-14","type":"journal-article","created":{"date-parts":[[2014,11,11]],"date-time":"2014-11-11T05:42:42Z","timestamp":1415684562000},"page":"514-519","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Effect of the Hepatitis C Virus Protease Inhibitor Faldaprevir on the Pharmacokinetics of an Oral Contraceptive Containing Ethinylestradiol and Levonorgestrel in Healthy Female Volunteers"],"prefix":"10.1128","volume":"59","author":[{"given":"John P.","family":"Sabo","sequence":"first","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Lang","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG, Biberach, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mabrouk","family":"Elgadi","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Canada Ltd.\/Lt\u00e9e, Burlington, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenglei","family":"Huang","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2458-9-34"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2010.03432.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.11.003"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.12.007"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.2147\/CPAA.S30338"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00787-10"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26276"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26386"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.08.040"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(13)61414-2"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-144-10-200605160-00004"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2013.772579"},{"key":"e_1_3_3_14_2","volume-title":"Abstr. 52nd Intersci Conf Antimicrob Agents Chemother","author":"Sabo JP","year":"2012","unstructured":"Sabo JP, Kashuba ADM, Ballow CH, Haschke M, Yong C, MacGregor TR, Li Y, Kort J. 2012. Cytochrome P450 (CYP) interactions with the HCV protease inhibitor BI201335 in healthy volunteers. Abstr. 52nd Intersci Conf Antimicrob Agents Chemother, abstr A-1248."},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26858"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.114.218081"},{"key":"e_1_3_3_17_2","volume-title":"Microgynon 30 ED: summary of product characteristics","author":"Bayer plc","year":"2014","unstructured":"Bayer plc. June 2014. Microgynon 30 ED: summary of product characteristics. Newbury, Berkshire, United Kingdom. http:\/\/www.mhra.gov.uk\/home\/groups\/spcpil\/documents\/spcpil\/con1415335698526.pdf."},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1177\/0091270005280851"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.0306-5251.2001.01521.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2000.00271.x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1177\/0091270011419855"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.104.000182"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-014-1711-0"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1023\/B:PHAM.0000033017.52484.81"},{"key":"e_1_3_3_25_2","volume-title":"ORTHO EVRA, Summary of product characteristics","author":"Janssen Ortho L","year":"2014","unstructured":"Janssen Ortho L. April 2014, posting date. ORTHO EVRA, Summary of product characteristics. Janssen Ortho LLC, Manati, Puerto Rico. http:\/\/www.orthoevra.com\/sites\/default\/files\/assets\/OrthoEvraPI.pdf."},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1177\/00912700122010023"},{"key":"e_1_3_3_27_2","volume-title":"A pooled analysis of two randomized, double-blind, placebo-controlled phase III trials (STARTVerso1 and 2) of faldaprevir plus pegylated interferon a-2a and ribavirin in treatment-naive patients with chronic hepatitis genotype-1 infection","author":"Jensen DM","year":"2013","unstructured":"Jensen DM, Asselah T, Dieterich D, Foster GR, Sulkowski MS, Zeuzem S, Mantry P, Moreno C, Ouzan D, Wright M, Morano LE, Buynak R, Bourli\u00e8re M, Hassanein T, Nishiguchi S, Kao J-H, Omata M, Paik SW, Wong DK, Tam E, Kaita K, Feinman SV, Stern JO, Garcia M, Quinson AM, Voss F, Gallivan J-P, Bocher WO, Ferenci P. 2013. A pooled analysis of two randomized, double-blind, placebo-controlled phase III trials (STARTVerso1 and 2) of faldaprevir plus pegylated interferon a-2a and ribavirin in treatment-naive patients with chronic hepatitis genotype-1 infection, abstr 1088. 64th Annu Meet Am Assoc Study Liver Dis, Washington, DC, 1 to 5 November 2013."},{"key":"e_1_3_3_28_2","volume-title":"STARTVerso3: a randomized, double-blind, placebo-controlled phase III trial of faldaprevir in combination with pegylated interferon alpha-2a and ribavirin in treatment-experienced patients with chronic HCV genotype-1 infection","author":"Jacobson IM","year":"2013","unstructured":"Jacobson IM, Asselah T, Ferenci P, Foster GR, Jensen DM, Negro F, Mantry P, Wright D, Forns X, Garcia-Samaniego J, Oliveira C, Carvalho A, Forton D, Agarwal K, Arasteh K, Cooper C, Ghesquiere W, Dufour J-F, Sakai Y, Tanaka Y, Stern JO, Sha N, Boecher WO, Steinmann G, Quinson AM. 2013. STARTVerso3: a randomized, double-blind, placebo-controlled phase III trial of faldaprevir in combination with pegylated interferon alpha-2a and ribavirin in treatment-experienced patients with chronic HCV genotype-1 infection, abstr 1100. 64th Annu Meet Am Assoc Study Liver Dis, Washington, DC, 1 to 5 November 2013."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.03589-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.03589-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T22:56:37Z","timestamp":1645484197000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.03589-14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["10.1128\/AAC.03589-14"],"URL":"https:\/\/doi.org\/10.1128\/aac.03589-14","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1]]},"assertion":[{"value":"2014-07-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-10-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-12-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}