{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T18:07:35Z","timestamp":1777572455508,"version":"3.51.4"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2001,3,1]],"date-time":"2001-03-01T00:00:00Z","timestamp":983404800000},"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":[[2001,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The antifungal efficacy, safety, and pharmacokinetics of posaconazole (SCH 56592) (POC) were investigated in treatment and prophylaxis of primary pulmonary aspergillosis due to\n            <jats:italic>Aspergillus fumigatus<\/jats:italic>\n            in persistently neutropenic rabbits. Antifungal therapy consisted of POC at 2, 6, and 20 mg\/kg of body weight per os; itraconazole (ITC) at 2, 6, and 20 mg\/kg per os; or amphotericin B (AMB) at 1 mg\/kg intravenously. Rabbits treated with POC showed a significant improvement in survival and significant reductions in pulmonary infarct scores, total lung weights, numbers of pulmonary CFU per gram, numbers of computerized-tomography-monitored pulmonary lesions, and levels of galactomannan antigenemia. AMB and POC had comparable therapeutic efficacies by all parameters. By comparison, animals treated with ITC had no significant changes in outcome variables in comparison to those of untreated controls (UC). Rabbits receiving prophylactic POC at all dosages showed a significant reduction in infarct scores, total lung weights, and organism clearance from lung tissue in comparison to results for UC (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.01). There was dosage-dependent microbiological clearance of\n            <jats:italic>A. fumigatus<\/jats:italic>\n            from lung tissue in response to POC. Serum creatinine levels were greater (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.01) in AMB-treated animals than in UC and POC- or ITC-treated rabbits. There was no elevation of serum hepatic transaminase levels in POC- or ITC-treated rabbits. The pharmacokinetics of POC and ITC in plasma demonstrated dose dependency after multiple dosing. The 2-, 6-, and 20-mg\/kg dosages of POC maintained plasma drug levels above the MICs for the entire 24-h dosing interval. In summary, POC at \u22656 mg\/kg\/day per os generated sustained concentrations in plasma of \u22651 \u03bcg\/ml that were as effective in the treatment and prevention of invasive pulmonary aspergillosis as AMB at 1 mg\/kg\/day and more effective than cyclodextrin ITC at \u22656 mg\/kg\/day per os in persistently neutropenic rabbits.\n          <\/jats:p>","DOI":"10.1128\/aac.45.3.857-869.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:06:42Z","timestamp":1027764402000},"page":"857-869","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":149,"title":["Antifungal Activity and Pharmacokinetics of Posaconazole (SCH 56592) in Treatment and Prevention of Experimental Invasive Pulmonary Aspergillosis: Correlation with Galactomannan Antigenemia"],"prefix":"10.1128","volume":"45","author":[{"given":"Ruta","family":"Petraitiene","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vidmantas","family":"Petraitis","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas H.","family":"Groll","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tin","family":"Sein","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Piscitelli","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Pharmacokinetics Research Laboratory, Pharmacy Department,2 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myrna","family":"Candelario","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aida","family":"Field-Ridley","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nilo","family":"Avila","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Department of Radiology,3 Warren Grant Magnuson Clinical Center and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Bacher","sequence":"additional","affiliation":[{"name":"<!--label omitted: 4-->Surgery Service, Veterinary Resources Program, Office of Research Services,4 National Institutes of Health, Bethesda, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Walsh","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,1"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.5.1159-1162.2000"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.3.518"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.1093\/clinids\/14.Supplement_1.S43","article-title":"Opportunistic mycoses in the immunocompromised host: experience at a cancer center and review.","volume":"14","author":"Anaissie E.","year":"1992","unstructured":"Anaissie E. 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