{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T10:20:11Z","timestamp":1774866011854,"version":"3.50.1"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2004,4,1]],"date-time":"2004-04-01T00:00:00Z","timestamp":1080777600000},"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":[[2004,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Ravuconazole is a new antifungal triazole with broad-spectrum activity and a long half-life in plasma. We studied the antifungal efficacy, safety, and pharmacokinetics of ravuconazole lysine phosphoester in escalating dosages for the treatment of invasive pulmonary aspergillosis due to\n            <jats:italic>Aspergillus fumigatus<\/jats:italic>\n            in persistently neutropenic rabbits. Treatment groups consisted of rabbits treated with ravuconazole at 2.5 (RVC2.5), 5 (RVC5), and 10 (RVC10) mg\/kg of body weight\/day, rabbits treated with amphotericin B (AMB) at 1 mg\/kg\/day, or untreated controls. There was a dose-dependent reduction of pulmonary residual fungal burden (CFU per gram) in RVC5-, RVC10-, and AMB-treated rabbits in comparison to untreated controls (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.01,\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001, and\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.01, respectively). These findings correlated with progressive galactomannan antigenemia in untreated controls and the RVC2.5-treated rabbits, a lower galactomannan index (GMI) in RVC5- and RVC10-treated rabbits, and a similarly low GMI in AMB-treated rabbits (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.01). Rabbits treated with RVC5, RVC10, and AMB also showed a reduction of organism-mediated pulmonary injury, as measured by infarct scores and lung weights, in comparison to untreated controls (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001). These results were supported by decreased pulmonary infiltrates detected by computed tomography in RVC5- and RVC10-treated rabbits in comparison to untreated controls (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05). Survival throughout the entire study was achieved in 95% of RVC5-treated rabbits (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001), 85% of RVC10-treated rabbits (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001), and 50% of AMB-treated rabbits (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05) in comparison to none of the untreated controls. Ravuconazole showed linear plasma pharmacokinetics and a large volume of distribution while maintaining concentrations in plasma above the MIC throughout the dosing interval. There was no evidence of hepatotoxicity or nephrotoxicity among ravuconazole-treated animals. Intravenously administered ravuconazole lysine phosphoester showed dose-dependent efficacy and an excellent safety profile for the treatment of invasive pulmonary aspergillosis in persistently neutropenic rabbits.\n          <\/jats:p>","DOI":"10.1128\/aac.48.4.1188-1196.2004","type":"journal-article","created":{"date-parts":[[2004,3,26]],"date-time":"2004-03-26T20:18:01Z","timestamp":1080332281000},"page":"1188-1196","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":38,"title":["Efficacy, Safety, and Plasma Pharmacokinetics of Escalating Dosages of Intravenously Administered Ravuconazole Lysine Phosphoester for Treatment of Experimental Pulmonary Aspergillosis in Persistently Neutropenic Rabbits"],"prefix":"10.1128","volume":"48","author":[{"given":"Ruta","family":"Petraitiene","sequence":"first","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vidmantas","family":"Petraitis","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caron A.","family":"Lyman","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas H.","family":"Groll","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Mickiene","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne","family":"Peter","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Bacher","sequence":"additional","affiliation":[{"name":"Surgery Service, Veterinary Resources Program, Office of Research Services"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin","family":"Roussillon","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Hemmings","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derrek","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nilo A.","family":"Avila","sequence":"additional","affiliation":[{"name":"Department of Radiology, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/14.Supplement_1.S43"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.4.1193-1199.2003"},{"key":"e_1_3_1_4_2","first-page":"555","volume":"3","year":"2002","unstructured":"Arikan, S., and J. 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