{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:39:24Z","timestamp":1791383964766,"version":"4.3.3"},"reference-count":0,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2002,1,27]],"date-time":"2002-01-27T00:00:00Z","timestamp":1012089600000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2002,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Modafinil has been reported to produce a concentration\u2010related induction of CYP3A4\/5 activity in vitro in primary cultures of human hepatocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>Our objective was to determine whether the pharmacokinetics of steady\u2010state ethinyl estradiol (INN, ethinylestradiol) and single\u2010dose triazolam were altered after 4 weeks of modafinil treatment in volunteers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a placebo\u2010controlled, single\u2010blind, single\u2010period study in 41 female subjects who were receiving long\u2010term treatment with an oral contraceptive that contained ethinyl estradiol (0.035 mg) and norgestimate (0.180\u20130.250 mg). Pharmacokinetic profiles for ethinyl estradiol and for a single oral dose of triazolam (0.125 mg) were obtained the day before initiation of treatment with modafinil (200 mg for 7 days, followed by 400 mg for 21 days) or placebo (28 days). A second dose of triazolam was administered with the final dose of modafinil, and pharmacokinetic profiling was repeated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The modafinil treatment group had a marked decrease in maximum observed plasma concentrations and areas under the plasma concentration\u2013time curve for triazolam relative to placebo, with a much smaller decrease in these parameters for ethinyl estradiol. The half\u2010life of triazolam was also decreased, but the half\u2010life of ethinyl estradiol did not appear to be affected by treatment with modafinil.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Modafinil induced CYP3A4\/5 activity in humans in vivo, suggesting that there is potential for metabolic drug\u2010drug interactions between modafinil and substrates of CYP3A4\/5. However, the induction appeared to be more gastrointestinal than hepatic in nature. Therefore significant metabolic drug\u2010drug interactions are most likely to occur with compounds (such as triazolam) that undergo significant gastrointestinal CYP3A4\/5\u2010mediated first\u2010pass metabolism.<\/jats:p><jats:p><jats:italic>Clinical Pharmacology &amp; Therapeutics<\/jats:italic> (2002) <jats:bold>71<\/jats:bold>, 46\u201356; doi: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1067\/mcp.2002.121217\">10.1067\/mcp.2002.121217<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1067\/mcp.2002.121217","type":"journal-article","created":{"date-parts":[[2002,8,24]],"date-time":"2002-08-24T22:14:26Z","timestamp":1030227266000},"page":"46-56","source":"Crossref","is-referenced-by-count":52,"title":["Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers"],"prefix":"10.1111","volume":"71","author":[{"suffix":"Jr","given":"Philmore","family":"Robertson","sequence":"first","affiliation":[{"name":"Departments of Drug Disposition, Biostatistics, and Medical Affairs, Cephalon, Inc."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward T.","family":"Hellriegel","sequence":"additional","affiliation":[{"name":"Departments of Drug Disposition, Biostatistics, and Medical Affairs, Cephalon, Inc."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Arora","sequence":"additional","affiliation":[{"name":"Departments of Drug Disposition, Biostatistics, and Medical Affairs, Cephalon, Inc."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Nelson","sequence":"additional","affiliation":[{"name":"Departments of Drug Disposition, Biostatistics, and Medical Affairs, Cephalon, Inc."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,1,27]]},"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1067\/mcp.2002.121217","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T10:28:02Z","timestamp":1700303282000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1067\/mcp.2002.121217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,1]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2002,1]]}},"alternative-id":["10.1067\/mcp.2002.121217"],"URL":"https:\/\/doi.org\/10.1067\/mcp.2002.121217","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,1]]}}}