{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T10:34:10Z","timestamp":1782902050140,"version":"3.54.5"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,3,7]],"date-time":"2013-03-07T00:00:00Z","timestamp":1362614400000},"content-version":"vor","delay-in-days":1892,"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":[[2008,1]]},"abstract":"<jats:p>A randomized, placebo\u2013controlled (with respect to voriconazole), 2\u2010period, multiple\u2010dose intragroup fixed\u2010dose sequence study was conducted in 34 healthy male subjects to evaluate the interactions between voriconazole (triazole antifungal agent) and efavirenz (reverse transcriptase inhibitor). In period 1, subjects received 200 mg twice\u2010daily (bid) voriconazole (n = 17) or placebo (n = 17) for 3 days (400\u2010mg bid loading doses on day 1). In period 2, following a 7\u2010day washout, subjects received 400 mg once\u2010daily (qd) efavirenz alone for 10 days (days 11\u201320). Then efavirenz was coadministered with 200 mg bid voriconazole or placebo for the next 9 days (days 21\u201329). Serial plasma voriconazole and efavirenz concentrations were measured on days 3, 19, and 29, and the safety data were collected throughout the study. The 400\u2010mg qd efavirenz dose substantially reduced the steady\u2010state mean voriconazole area under the curve over the dosing interval (AUC<jats:sub><jats:italic>0\u201312<\/jats:italic><\/jats:sub>) by 80% (90% confidence interval [CI], 75%\u201384%) and peak concentration (C<jats:sub><jats:italic>max<\/jats:italic><\/jats:sub>) by 66% (90% CI, 57%\u201373%). The decrease in voriconazole exposure during coadministration is probably mainly due to the induction of CYP2C19 and CYP2C9 by efavirenz. The 200 mg bid voriconazole increased the steady\u2010state mean AUC<jats:sub><jats:italic>0\u201324<\/jats:italic><\/jats:sub> and C<jats:sub><jats:italic>max<\/jats:italic><\/jats:sub> of efavirenz by 43% (90% CI, 36%\u201351%) and 37% (90% CI, 29%\u201346%), respectively. The increase in efavirenz exposure during coadministration is probably due to the inhibition of CYP3A4 by voriconazole. Coadministration of 200 mg bid voriconazole with 400 mg (or higher) qd efavirenz is contraindicated due to the clinically significant effect of efavirenz on voriconazole pharmacokinetics.<\/jats:p>","DOI":"10.1177\/0091270007309703","type":"journal-article","created":{"date-parts":[[2007,11,20]],"date-time":"2007-11-20T02:18:26Z","timestamp":1195525106000},"page":"73-84","source":"Crossref","is-referenced-by-count":54,"title":["Pharmacokinetic Interaction Between Voriconazole and Efavirenz at Steady State in Healthy Male Subjects"],"prefix":"10.1002","volume":"48","author":[{"given":"Ping","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grover","family":"Foster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rober R.","family":"LaBadie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari 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