{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T01:46:22Z","timestamp":1771724782966,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2008,2,21]],"date-time":"2008-02-21T00:00:00Z","timestamp":1203552000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2008,4]]},"abstract":"<jats:sec><jats:label\/><jats:p> <jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold> <\/jats:p><jats:p>\u2022\u2003Voriconazole, a broad\u2010spectrum antifungal drug, is a substrate and inhibitor of CYP2C19 and CYP3A4 isozymes.<\/jats:p><jats:p>\u2022\u2003Ethinyl oestradiol and norethindrone, components of the combination oral contraceptive drug Ortho\u2010Novum\u00ae 1\/35, also are substrates of cytochrome P450 CYP2C19 and CYP3A4 isozymes.<\/jats:p><jats:p>\u2022\u2003Because co\u2010administration of voriconazole and Ortho\u2010Novum\u00ae 1\/35 could potentially result in pharmacokinetic interactions that increase systemic exposure of one or both drugs to unsafe levels, clinical studies are needed to define better the two\u2010way pharmacokinetic interaction between these drugs.<\/jats:p><jats:p> <jats:bold>WHAT THIS STUDY ADDS<\/jats:bold> <\/jats:p><jats:p>\u2022\u2003Although co\u2010administered voriconazole and oral contraceptive did result in increased systemic exposures of all three drugs relative to respective monotherapy, co\u2010administered treatment was generally safe and well tolerated.<\/jats:p><jats:p>\u2022\u2003It is recommended, however, that patients receiving co\u2010administered voriconazole and oral contraceptives be monitored for the development of adverse events commonly associated with these medications.<\/jats:p><\/jats:sec><jats:sec><jats:title>AIM<\/jats:title><jats:p>To assess the two\u2010way pharmacokinetic interaction between voriconazole and Ortho\u2010Novum\u00ae 1\/35, an oral contraceptive containing norethindrone 1\u2003mg and ethinyl oestradiol 35\u2003\u03bcg.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>In this open\u2010label, three\u2010period, fixed\u2010sequence study, 16\u2003healthy females received voriconazole (400\u2003mg q12\u2003h, day 1; 200\u2003mg q12\u2003h, days 2\u20134) (period 1), oral contraceptive (q24\u2003h, days 12\u201332) (period 2), and combination voriconazole (400\u2003mg q12\u2003h, day 57; 200\u2003mg q12\u2003h, days 58\u201360) and oral contraceptive (q24\u2003h, days 40\u201360) (period 3).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Voriconazole geometric mean AUC<jats:sub>\u03c4<\/jats:sub> and <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> increased 46% (12\u2003682\u201318\u2003495\u2003ng\u2003h\u2003ml<jats:sup>\u22121<\/jats:sup>; 90% confidence interval [CI] 32, 61) and 14% (2485\u20132840\u2003ng\u2003ml<jats:sup>\u22121<\/jats:sup>; 90% CI 3, 27), respectively, when co\u2010administered with oral contraceptive <jats:italic>vs.<\/jats:italic> voriconazole alone. Ethinyl oestradiol geometric mean AUC<jats:sub>\u03c4<\/jats:sub> and <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> increased 61% (1031\u20131657\u2003ng\u2003h\u2003ml<jats:sup>\u22121<\/jats:sup>; 90% CI 50, 72) and 36% (119\u2013161\u2003ng\u2003ml<jats:sup>\u22121<\/jats:sup>; 90% CI 28, 45), respectively, and norethindrone geometric mean AUC<jats:sub>\u03c4<\/jats:sub> and <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> increased 53% (116\u2013177\u2003ng\u2003h\u2003ml<jats:sup>\u22121<\/jats:sup>; 90% CI 44, 64) and 15% (18\u201320\u2003ng\u2003ml<jats:sup>\u22121<\/jats:sup>; 90% CI 3, 28), respectively, during voriconazole co\u2010administration <jats:italic>vs.<\/jats:italic> oral contraceptive alone. Neither ethinyl oestradiol nor norethindrone levels were reduced in subjects following voriconazole co\u2010administration. Adverse events (AEs) were generally mild, occurring less in subjects receiving voriconazole alone (36 events) <jats:italic>vs.<\/jats:italic> oral contraceptive alone (88 events) or combination treatment (68 events); four subjects experienced a severe AE.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Co\u2010administration of voriconazole and oral contraceptive increased systemic exposures of all analytes relative to respective monotherapy. Although generally safe and well tolerated, it is recommended that patients receiving co\u2010administered voriconazole and oral contraceptive be monitored for development of AEs commonly associated with these medications.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2125.2007.03084.x","type":"journal-article","created":{"date-parts":[[2008,2,21]],"date-time":"2008-02-21T10:26:15Z","timestamp":1203589575000},"page":"531-539","source":"Crossref","is-referenced-by-count":42,"title":["Pharmacokinetics and tolerability of voriconazole and a combination oral contraceptive co\u2010administered in healthy female subjects"],"prefix":"10.1111","volume":"65","author":[{"given":"Emma","family":"Andrews","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bharat D.","family":"Damle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annie","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grover","family":"Foster","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Penelope","family":"Crownover","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"LaBadie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Glue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,2,21]]},"reference":[{"key":"e_1_2_6_2_2","volume-title":"Vfend\u00ae. 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