{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:15:44Z","timestamp":1791260144683,"version":"4.1.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"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":[[2012,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Posaconazole has an important role in the prophylaxis and salvage treatment of invasive fungal infections (IFIs), although poor and variable bioavailability remains an important clinical concern. Therapeutic drug monitoring of posaconazole concentrations has remained contentious, with the use of relatively small patient cohorts in previous studies hindering the assessment of exposure-response relationships. This multicenter retrospective study aimed to investigate relationships between posaconazole concentration and clinical outcomes and adverse events and to assess clinical factors and drug interactions that may affect posaconazole concentrations. Medical records were reviewed for patients who received posaconazole and had \u22651 concentration measured at six hospitals in Australia. Data from 86 patients with 541 posaconazole concentrations were included in the study. Among 72 patients taking posaconazole for prophylaxis against IFIs, 12 patients (17%) developed a breakthrough fungal infection; median posaconazole concentrations were significantly lower than in those who did not develop fungal infection (median [range], 289 [50 to 471] ng\/ml versus 485 [0 to 2,035] ng\/ml;\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.01). The median posaconazole concentration was a significant predictor of breakthrough fungal infection via binary logistic regression (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05). A multiple linear regression analysis identified a number of significant drug interactions associated with reduced posaconazole exposure, including coadministration with proton pump inhibitors, metoclopramide, phenytoin or rifampin, and the H\n                    <jats:sub>2<\/jats:sub>\n                    antagonist ranitidine (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.01). Clinical factors such as mucositis, diarrhea, and the early posttransplant period in hematopoietic stem cell transplant recipients were also associated with reduced posaconazole exposure (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.01). Low posaconazole concentrations are common and are associated with breakthrough fungal infection, supporting the utility of monitoring posaconazole concentrations to ensure optimal systemic exposure.\n                  <\/jats:p>","DOI":"10.1128\/aac.00802-12","type":"journal-article","created":{"date-parts":[[2012,8,13]],"date-time":"2012-08-13T22:34:33Z","timestamp":1344897273000},"page":"5503-5510","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":174,"title":["Multicenter Study of Posaconazole Therapeutic Drug Monitoring: Exposure-Response Relationship and Factors Affecting Concentration"],"prefix":"10.1128","volume":"56","author":[{"given":"Michael J.","family":"Dolton","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, University of Sydney, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Ray","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Toxicology, SydPath, St. Vincent's Hospital, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon C.-A.","family":"Chen","sequence":"additional","affiliation":[{"name":"Centre for Infectious Diseases and Microbiology and the University of Sydney, Westmead Hospital, Westmead, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kingsley","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Westmead Hospital, Westmead, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Pont","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Sydney, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"McLachlan","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Sydney, Sydney, Australia"},{"name":"Centre for Education and Research on Ageing, Concord Repatriation General Hospital, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1212\/WNL.63.10_suppl_4.S3","article-title":"Pharmacogenetics and enzyme induction\/inhibition properties of antiepileptic drugs","volume":"63","author":"Anderson GD","year":"2004","unstructured":"AndersonGD. 2004. 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Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer\/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC\/MSG) Consensus Group. Clin. Infect. Dis. 46:1813\u20131821.","journal-title":"Clin. Infect. Dis."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05900-11"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-011-1288-9"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2011.05.010"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1124\/dmd.32.2.267","article-title":"Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of posaconazole (Noxafil)","volume":"32","author":"Ghosal A","year":"2004","unstructured":"GhosalA. 2004. Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of posaconazole (Noxafil). Drug Metab. Dispos. 32:267\u2013271.","journal-title":"Drug Metab. 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