{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T04:46:43Z","timestamp":1768279603548,"version":"3.49.0"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2016,5,1]],"date-time":"2016-05-01T00:00:00Z","timestamp":1462060800000},"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":[[2016,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We studied the pharmacokinetics and efficacy of the broad-spectrum triazole isavuconazole for the treatment of experimental invasive pulmonary aspergillosis (IPA) in persistently neutropenic rabbits. Treatment started 24 h after endotracheal administration of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Aspergillus fumigatus<\/jats:named-content>\n            inoculum; study subjects included rabbits receiving orally administered prodrug isavuconazonium sulfate (BAL8557) equivalent to active moiety isavuconazole (ISA; BAL4815) at 20 (ISA20), 40 (ISA40), and 60 (ISA60) mg\/kg (of body weight)\/day, with an initial loading dose of 90 mg\/kg (ISA90), and untreated rabbits (UC). There were significant concentration-dependent reductions of residual fungal burden (log CFU\/gram) and of organism-mediated pulmonary injury, lung weights, and pulmonary infarct scores in ISA40- and ISA60-treated rabbits in comparison to those of UC (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001). ISA20-treated (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05), ISA40-treated, and ISA60-treated (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001) rabbits demonstrated significantly prolonged survival in comparison to that of UC. ISA40- and ISA60-treated animals demonstrated a significant decline of serum (1\u21923)-\u03b2-\n            <jats:sc>d<\/jats:sc>\n            -glucan levels (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05) and galactomannan indices (GMIs) during therapy following day 4 in comparison to progressive GMIs of UC (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.01). There also were significantly lower concentration-dependent GMIs in bronchoalveolar lavage (BAL) fluid from ISA40- and ISA60-treated rabbits (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001). There was a direct correlation between isavuconazole plasma area under the concentration-time curve from 0 to 24 h (AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            ) and residual fungal burdens in lung tissues, pulmonary infarct scores, and total lung weights. In summary, rabbits treated with isavuconazole at 40 and 60 mg\/kg\/day demonstrated significant dose-dependent reduction of residual fungal burden, decreased pulmonary injury, prolonged survival, lower GMIs in serum and BAL fluid, and lower serum (1\u21923)-\u03b2-\n            <jats:sc>d<\/jats:sc>\n            -glucan levels.\n          <\/jats:p>","DOI":"10.1128\/aac.02665-15","type":"journal-article","created":{"date-parts":[[2016,2,17]],"date-time":"2016-02-17T03:49:32Z","timestamp":1455680972000},"page":"2718-2726","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":38,"title":["Pharmacokinetics and Concentration-Dependent Efficacy of Isavuconazole for Treatment of Experimental Invasive Pulmonary Aspergillosis"],"prefix":"10.1128","volume":"60","author":[{"given":"Vidmantas","family":"Petraitis","sequence":"first","affiliation":[{"name":"Transplantation-Oncology Infectious Diseases, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruta","family":"Petraitiene","sequence":"additional","affiliation":[{"name":"Transplantation-Oncology Infectious Diseases, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patriss W.","family":"Moradi","sequence":"additional","affiliation":[{"name":"Transplantation-Oncology Infectious Diseases, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gittel E.","family":"Strauss","sequence":"additional","affiliation":[{"name":"Transplantation-Oncology Infectious Diseases, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aspasia","family":"Katragkou","sequence":"additional","affiliation":[{"name":"Transplantation-Oncology Infectious Diseases, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura L.","family":"Kovanda","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc., Northbrook, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William W.","family":"Hope","sequence":"additional","affiliation":[{"name":"Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Transplantation-Oncology Infectious Diseases, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, New York, USA"},{"name":"Departments of Pediatrics and Microbiology &amp; Immunology, Weill Cornell Medicine of Cornell University, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/651263"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2014-206291"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"S255","DOI":"10.1080\/13693780902718339","article-title":"Risk stratification for invasive aspergillosis: early assessment of host susceptibility","volume":"47","author":"Patterson TF","year":"2009","unstructured":"Patterson TF. 2009. 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Isavuconazole (ISA) population pharmacokinetic modeling from phase 1 and phase 3 clinical trials and target attainment analysis, abstr A-697. 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