{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T10:36:23Z","timestamp":1789209383344,"version":"build-2803163510"},"reference-count":12,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,8,27]],"date-time":"2014-08-27T00:00:00Z","timestamp":1409097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Ivacaftor is approved in the USA for the treatment of cystic fibrosis (CF) in patients with a <jats:italic>G551D\u2010CFTR<\/jats:italic> mutation or one of eight other <jats:italic>CFTR<\/jats:italic> mutations. A series of in vitro experiments conducted early in the development of ivacaftor indicated ivacaftor and metabolites may have the potential to inhibit cytochrome P450 (CYP) 2C8, CYP2C9, CYP3A, and CYP2D6, as well as P\u2010glycoprotein (P\u2010gp). Based on these results, a series of clinical drug\u2010drug interaction (DDI) studies were conducted to evaluate the effect of ivacaftor on sensitive substrates of CYP2C8 (rosiglitazone), CYP3A (midazolam), CYP2D6 (desipramine), and P\u2010gp (digoxin). In addition, a DDI study was conducted to evaluate the effect of ivacaftor on a combined oral contraceptive, as this is considered an important comedication in CF patients. The results indicate ivacaftor is a weak inhibitor of CYP3A and P\u2010gp, but has no effect on CYP2C8 or CYP2D6. Ivacaftor caused non\u2010clinically significant increases in ethinyl estradiol and norethisterone exposure. Based on these results, caution and appropriate monitoring are recommended when concomitant substrates of CYP2C9, CYP3A and\/or P\u2010gp are used during treatment with ivacaftor, particularly drugs with a narrow therapeutic index, such as warfarin.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcph.377","type":"journal-article","created":{"date-parts":[[2014,8,7]],"date-time":"2014-08-07T20:57:35Z","timestamp":1407445055000},"page":"56-62","source":"Crossref","is-referenced-by-count":54,"title":["Clinical drug\u2010drug interaction assessment of ivacaftor as a potential inhibitor of cytochrome P450 and P\u2010glycoprotein"],"prefix":"10.1002","volume":"55","author":[{"given":"Sarah M.","family":"Robertson","sequence":"first","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated Boston  MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Luo","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated Boston  MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeraj","family":"Dubey","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated Boston  MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chonghua","family":"Li","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated Boston  MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajit B.","family":"Chavan","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated Boston  MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey S.","family":"Gilmartin","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated Boston  MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Higgins","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals (Europe) Limited Milton Park UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Mahnke","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated Boston  MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,8,27]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2007.05.001"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2011.12.005"},{"key":"e_1_2_5_4_1","unstructured":"Kalydeco\u00ae 2014 Vertex Pharmaceuticals Inc Boston MA"},{"key":"e_1_2_5_5_1","unstructured":"US Food and Drug Administration 2012 Drug Interaction Studies \u2014Study Design Data Analysis Implications for Dosing and Labeling Recommendations February 2012"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2012.12.011"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1185\/03007995.2011.595780"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.2165\/11590240-000000000-00000"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2007.09.025"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0010-7824(90)90093-B"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2007.03084.x"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270011419855"},{"key":"e_1_2_5_13_1","unstructured":"Emend\u00ae 2013 Merck & Co. Inc Whitehouse Station NJ"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcph.377","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.377","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T20:15:05Z","timestamp":1696364105000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.377"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,27]]},"references-count":12,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["10.1002\/jcph.377"],"URL":"https:\/\/doi.org\/10.1002\/jcph.377","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,27]]}}}