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For voriconazole, time to reach steady state can vary from 5\u20137 days, not optimal for critically ill patients. We developed a population pharmacokinetic\/pharmacodynamic model\u2010based approach to predict doses that can maximize the net benefit (probability of efficacy\u2010probability of adverse events) and ensure therapeutic concentrations, early on during treatment. The label\u2010recommended 200\u2009mg voriconazole dose resulted in attainment of targeted concentrations in \u226580% patients in the case of <jats:italic>Candida spp<\/jats:italic>. infections, as compared to only 40\u201350% patients, with net benefit ranging from 5.8\u201361.8%, in the case of <jats:italic>Aspergillus spp<\/jats:italic>. infections. Voriconazole doses of 300\u2013600\u2009mg were found to maximize the net benefit up to 51\u201366.7%, depending on the clinical phenotype (due to CYP2C19 status and pantoprazole use) of the patient and type of <jats:italic>Aspergillus<\/jats:italic> infection.<\/jats:p>","DOI":"10.1002\/cpt.1012","type":"journal-article","created":{"date-parts":[[2018,1,10]],"date-time":"2018-01-10T12:24:30Z","timestamp":1515587070000},"page":"957-965","source":"Crossref","is-referenced-by-count":56,"title":["Optimization of Voriconazole Therapy for the Treatment of Invasive Fungal Infections in Adults"],"prefix":"10.1111","volume":"104","author":[{"given":"Naveen","family":"Mangal","sequence":"first","affiliation":[{"name":"Center for Pharmacometrics &amp; Systems Pharmacology, College of Pharmacy University of Florida Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issam S.","family":"Hamadeh","sequence":"additional","affiliation":[{"name":"Levine Cancer Institute, Department of Cancer Pharmacology Charlotte North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan J.","family":"Arwood","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa H.","family":"Cavallari","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanay S.","family":"Samant","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation East Hanover New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth P.","family":"Klinker","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jurgen","family":"Bulitta","sequence":"additional","affiliation":[{"name":"Center for Pharmacometrics &amp; Systems Pharmacology, College of Pharmacy University of Florida Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Center for Pharmacometrics &amp; Systems Pharmacology, College of Pharmacy University of Florida Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,2,13]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1086\/318483"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.18.1.44-69.2005"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/525258"},{"key":"e_1_2_9_4_1","unstructured":"VFEND P.Package insert. 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