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Compared with each drug alone, coadministration with isavuconazole changed the area under the concentration\u2010time curves (AUC<jats:sub>\u221e<\/jats:sub>) and maximum concentrations (C<jats:sub>max<\/jats:sub>) as follows: bupropion, AUC<jats:sub>\u221e<\/jats:sub> reduced 42%, C<jats:sub>max<\/jats:sub> reduced 31%; repaglinide, AUC<jats:sub>\u221e<\/jats:sub> reduced 8%, C<jats:sub>max<\/jats:sub> reduced 14%; caffeine, AUC<jats:sub>\u221e<\/jats:sub> increased 4%, C<jats:sub>max<\/jats:sub> reduced 1%; dextromethorphan, AUC<jats:sub>\u221e<\/jats:sub> increased 18%, C<jats:sub>max<\/jats:sub> increased 17%; R\u2010methadone, AUC<jats:sub>\u221e<\/jats:sub> reduced 10%, C<jats:sub>max<\/jats:sub> increased 3%; S\u2010methadone, AUC<jats:sub>\u221e<\/jats:sub> reduced 35%, C<jats:sub>max<\/jats:sub> increased 1%. In all studies, there were no deaths, 1 serious adverse event (dextromethorphan study; perioral numbness, numbness of right arm and leg), and adverse events leading to study discontinuation were rare. Thus, isavuconazole is a mild inducer of CYP2B6 but does not appear to affect CYP1A2\u2010, CYP2C8\u2010, or CYP2D6\u2010mediated metabolism.<\/jats:p>","DOI":"10.1002\/cpdd.281","type":"journal-article","created":{"date-parts":[[2016,6,8]],"date-time":"2016-06-08T08:59:18Z","timestamp":1465376358000},"page":"54-65","source":"Crossref","is-referenced-by-count":40,"title":["Pharmacokinetic Effects of Isavuconazole Coadministration With the Cytochrome P450 Enzyme Substrates Bupropion, Repaglinide, Caffeine, Dextromethorphan, and Methadone in Healthy Subjects"],"prefix":"10.1002","volume":"6","author":[{"given":"Takao","family":"Yamazaki","sequence":"first","affiliation":[{"name":"Astellas Pharma Global Development, Inc  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Desai","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Goldwater","sequence":"additional","affiliation":[{"name":"PAREXEL  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Han","sequence":"additional","affiliation":[{"name":"PAREXEL  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corrie","family":"Howieson","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahzad","family":"Akhtar","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Kowalski","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Lademacher","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Pearlman","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Rammelsberg","sequence":"additional","affiliation":[{"name":"Randstad Pharma  Deerfield IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Townsend","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,7,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2012.06.012"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004404"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.12703\/P6-81"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1652"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ571"},{"key":"e_1_2_7_7_1","first-page":"439","article-title":"Ergosterol biosynthesis in Aspergillus fumigatus: its relevance as an antifungal target and role in antifungal drug resistance","volume":"3","author":"Alcazar\u2010Fuoli L","year":"2012","journal-title":"Front Microbiol"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.2015.990382"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01159-9"},{"key":"e_1_2_7_10_1","unstructured":"PerfectJ CornelyO Ostrosky\u2010ZeichnerL et\u00a0al.Outcomes safety and tolerability of isavuconazole for the treatment of invasive fungal disease (phase 3 VITAL trial). 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