{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T02:50:38Z","timestamp":1772679038007,"version":"3.50.1"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,3,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              SF001 is a next-generation polyene antifungal drug in development, designed to have increased specificity to fungal ergosterol, which is absent in humans, and decreased binding to cholesterol. SF001 demonstrates long-acting, potent, broad-spectrum fungicidal activity. The goal of the current study was to determine the pharmacodynamic index and target of SF001 in an immunocompromised mouse model of invasive pulmonary aspergillosis against six\n              <jats:italic>Aspergillus fumigatus<\/jats:italic>\n              isolates. Minimum inhibitory concentration (MIC) values ranged from 0.5 to 2.0 mg\/L. Plasma and epithelial lining fluid (ELF) pharmacokinetics were performed following single intraperitoneal doses of 1, 4, 16, and 64 mg\/kg. Treatment efficacy was assessed with each of the six fungal isolates using daily doses of SF001 ranging from 0.25 to 64 mg\/kg\/day over a 96-h treatment duration. Efficacy was assessed by\n              <jats:italic>A. fumigatus<\/jats:italic>\n              quantitative PCR of conidial equivalents from lung homogenates. Nonlinear regression analysis using the Hill equation demonstrated that the 24-h exposure-response relationships for both plasma and ELF area under the concentration\/MIC and\n              <jats:italic>C<\/jats:italic>\n              <jats:sub>max<\/jats:sub>\n              \/MIC ratios were strong and relatively similar [coefficient of determination (\n              <jats:italic>R<\/jats:italic>\n              <jats:sup>2<\/jats:sup>\n              ) = 0.74\u20130.75). Exposure-response relationships included a median plasma 24-h\n              <jats:italic>C<\/jats:italic>\n              <jats:sub>max<\/jats:sub>\n              \/MIC target for stasis and 1-log kill endpoint of 0.5 and 0.6, respectively. The present studies demonstrated\n              <jats:italic>in vitro<\/jats:italic>\n              and\n              <jats:italic>in vivo<\/jats:italic>\n              SF001 potency against\n              <jats:italic>A. fumigatus<\/jats:italic>\n              . These results have potential relevance for SF001 clinical dose selection and evaluation of susceptibility breakpoints.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01631-23","type":"journal-article","created":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T14:01:27Z","timestamp":1707228087000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["<i>In vivo<\/i>\n            pharmacodynamic characterization of a next-generation polyene, SF001, in the invasive pulmonary aspergillosis mouse model"],"prefix":"10.1128","volume":"68","author":[{"given":"Alexander J.","family":"Lepak","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6527-1475","authenticated-orcid":true,"given":"Brian","family":"VanScoy","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Schenectady, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3172-0847","authenticated-orcid":false,"given":"Chris","family":"Rubino","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Schenectady, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2230-1125","authenticated-orcid":true,"given":"Paul G.","family":"Ambrose","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Schenectady, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7927-9950","authenticated-orcid":true,"given":"David R.","family":"Andes","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA"},{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin, USA"},{"name":"William S. 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