{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T04:53:52Z","timestamp":1764996832754},"reference-count":19,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2008,2,20]],"date-time":"2008-02-20T00:00:00Z","timestamp":1203465600000},"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\u2003Efavirenz 400\u2003mg q24\u2003h reduces exposure to voriconazole 200\u2003mg q12\u2003h when the two drugs are co\u2010administered.<\/jats:p><jats:p>\u2022\u2003Furthermore, voriconazole increases the systemic exposure of efavirenz.<\/jats:p><jats:p>\u2022\u2003Co\u2010administration was therefore initially contraindicated.<\/jats:p><jats:p> <jats:bold>WHAT THIS STUDY ADDS<\/jats:bold> <\/jats:p><jats:p>\u2022\u2003The doses of efavirenz and voriconazole can be adjusted to provide adequate exposure to both drugs when the two are co\u2010administered, without compromising safety.<\/jats:p><jats:p>\u2022\u2003Appropriate adjustment of doses for both drugs may thus represent an alternative to a mere contraindication.<\/jats:p><\/jats:sec><jats:sec><jats:title>AIMS<\/jats:title><jats:p>Co\u2010administration of standard\u2010dose voriconazole and efavirenz results in a substantial decrease in voriconazole levels, while concurrently increasing efavirenz levels. Hence, concomitant use of standard doses of these drugs was initially contraindicated. This study assessed different dose combinations of efavirenz and voriconazole, with the goal of attaining a dose combination that provides systemic exposures similar to standard\u2010dose monotherapy with each drug.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>This was an open\u2010label, four\u2010treatment, multiple\u2010dose, fixed\u2010sequence study in 16 healthy males. Steady\u2010state pharmacokinetics were assessed following two test treatments (voriconazole 300\u2003mg q12\u2003h + efavirenz 300\u2003mg q24\u2003h and voriconazole 400\u2003mg q12\u2003h + efavirenz 300\u2003mg q24\u2003h) and compared with standard\u2010dose monotherapy (voriconazole 200\u2003mg q12\u2003h or efavirenz 600\u2003mg q24\u2003h).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Dose adjustment to voriconazole 300\u2003mg q12\u2003h with efavirenz 300\u2003mg q24\u2003h decreased voriconazole area under the concentration\u2013time curve (AUC<jats:sub>\u03c4<\/jats:sub>) and maximum concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>), with changes of \u221255% [90% confidence interval (CI) \u221262, \u221245] and \u221236% (90% CI \u221249, \u221221), respectively, when compared with monotherapy. Voriconazole 400\u2003mg q12\u2003h plus efavirenz 300\u2003mg q24\u2003h decreased voriconazole AUC<jats:sub>\u03c4<\/jats:sub> (\u22127%; 90% CI \u221223, 13) and increased <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> (23%; 90% CI \u22121, 53), while increasing efavirenz AUC<jats:sub>\u03c4<\/jats:sub> (17%; 90% CI 6, 29) and not changing <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> when compared with the respective monotherapy regimens. No serious adverse events were observed with voriconazole plus efavirenz.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>When co\u2010administered, voriconazole dose should be increased to 400\u2003mg q12\u2003h and efavirenz dose decreased to 300\u2003mg q24\u2003h in order to provide systemic exposures similar to standard\u2010dose monotherapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2125.2007.03085.x","type":"journal-article","created":{"date-parts":[[2008,2,20]],"date-time":"2008-02-20T14:53:46Z","timestamp":1203519226000},"page":"523-530","source":"Crossref","is-referenced-by-count":26,"title":["Pharmacokinetic interactions of efavirenz and voriconazole in healthy volunteers"],"prefix":"10.1111","volume":"65","author":[{"given":"Bharat","family":"Damle","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"LaBadie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Penelope","family":"Crownover","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":[[2008,2,20]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3062.2002.t01-2-02002.x"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67490-9"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/322653"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.31.5.540"},{"key":"e_1_2_6_6_2","unstructured":"Sustiva\u00ae (efavirenz) prescribing information.Bristol\u2010Myers Squibb Company. 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