{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T21:55:28Z","timestamp":1783029328742,"version":"3.54.6"},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T00:00:00Z","timestamp":1711584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>VT-1598 is a novel fungal CYP51 inhibitor and 1-tetrazole-based antifungal drug candidate with improved selectivity minimizing off-target binding to and inhibition of human CYP450 enzymes. Data are presented from this first clinical study in the evaluation of the safety and pharmacokinetic (PK) of single ascending doses of 40, 80, 160, 320, and 640\u00a0mg VT-1598, comprising a 160\u00a0mg cohort in both fasting and fed states. Eight healthy adults per dose were randomized to receive either oral VT-1598 or placebo (3:1). Over the dose range, exposures were with relatively high variation. The maximum plasma concentrations (Cmax) for VT-1598 were 31.00\u2013279.4\u00a0ng\/ml and for its primary metabolite, VT-11134, were 27.80\u2013108.8\u00a0ng\/ml. The plasma area under the concentration\u2013time curve to the last measurable concentration (AUC0\u2013last) for VT-1598 were 116.1\u20134507 ng*h\/ml, and for VT-11134 were 1140\u20137156 ng*h\/ml. The dose proportionality was inconclusive based on the results of the power model. The peak concentration time (Tmax) was 4\u20135 h for VT-1598 and for VT-11134. Half-life was 103\u2013126 h for VT-11134. After food intake, Cmax of VT-1598 increased by 44% (geometric mean ratio (GMR), 1.44; 90%CI [0.691, 2.19]) and AUC0\u2013last by 126% (GMR, 2.26; 90%CI [1.09, 3.44]), while exposure of VT-11134 was decreased 23% for Cmax (GMR, 0.77; 90%CI [0.239, 1.31]) and unchanged for AUC0\u2013last (GMR, 1.02; 90%CI [0.701, 1.33]). Neither VT-1598 nor VT-11134 were detected in urine. No serious adverse events (AEs) or AEs leading to early termination were observed. The safety and PK profiles of VT-1598 support its further clinical development.<\/jats:p>","DOI":"10.1093\/mmy\/myae032","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T00:31:04Z","timestamp":1712190664000},"source":"Crossref","is-referenced-by-count":13,"title":["Safety and pharmacokinetics of antifungal agent VT-1598 and its primary metabolite, VT-11134, in healthy adult subjects: phase 1, first-in-human, randomized, double-blind, placebo-controlled study of single-ascending oral doses of VT-1598"],"prefix":"10.1093","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9621-8439","authenticated-orcid":false,"given":"Kenan","family":"Gu","sequence":"first","affiliation":[{"name":"Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Spitz","sequence":"additional","affiliation":[{"name":"Medical & Scientific Affairs, ICON plc , Blue Bell, PA 19422 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Hammett","sequence":"additional","affiliation":[{"name":"Department of Biometrics & Clinical Operations, The Emmes Company , Rockville, MD 20850 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Jaunarajs","sequence":"additional","affiliation":[{"name":"Department of Biometrics & Clinical Operations, The Emmes Company , Rockville, MD 20850 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varduhi","family":"Ghazaryan","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward P","family":"Garvey","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Mycovia Pharmaceuticals , Durham, NC, 27709 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Degenhardt","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Mycovia Pharmaceuticals , Durham, NC, 27709 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,3]]},"reference":[{"key":"2024042216511384500_bib1","article-title":"WHO fungal priority pathogens list to guide research, development and public health action","author":"World Health Organization (WHO)","year":"2022"},{"key":"2024042216511384500_bib2","doi-asserted-by":"crossref","first-page":"152247","DOI":"10.1016\/j.tox.2019.152247","article-title":"The classic azole antifungal drugs are highly potent 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