{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:37:26Z","timestamp":1791308246509,"version":"4.3.1"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2017,11,22]],"date-time":"2017-11-22T00:00:00Z","timestamp":1511308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100007705","name":"Astellas Pharma, Inc.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007705","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Isavuconazole, the active moiety of the water-soluble prodrug isavuconazonium sulfate, is a triazole antifungal agent for the treatment of invasive fungal infections. The purpose of this analysis was to characterize the isavuconazole exposure-response relationship for measures of efficacy and safety in patients with invasive aspergillosis and infections by other filamentous fungi from the SECURE clinical trial. Two hundred thirty-one patients who received the clinical dosing regimen and had exposure parameters were included in the analysis. The primary drug exposure parameters included were predicted trough steady-state plasma concentrations, predicted trough concentrations after 7 and 14 days of drug administration, and area under the curve estimated at steady state (AUCss). The exposure parameters were analyzed against efficacy endpoints that included all-cause mortality through day 42 in the intent-to-treat (ITT) and modified ITT populations, data review committee (DRC)-adjudicated overall response at end of treatment (EOT), and DRC-adjudicated clinical response at EOT. The safety endpoints analyzed were elevated or abnormal alanine aminotransferase, increased aspartate aminotransferase, and a combination of the two. The endpoints were analyzed using logistic regression models. No statistically significant relationship (\n            <jats:italic>P<\/jats:italic>\n            &gt; 0.05) was found between isavuconazole exposure and either efficacy or safety endpoints. The lack of association between exposure and efficacy indicates that the isavuconazole exposures achieved by clinical dosing were appropriate for treating the infecting organisms in the SECURE study and that increases in alanine or aspartate aminotransferase were not related to increase in exposures. Without a clear relationship, there is no current clinical evidence for recommending routine therapeutic drug monitoring for isavuconazole.\n          <\/jats:p>","DOI":"10.1128\/aac.01034-17","type":"journal-article","created":{"date-parts":[[2017,9,19]],"date-time":"2017-09-19T00:40:23Z","timestamp":1505781623000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":115,"title":["Exposure-Response Relationships for Isavuconazole in Patients with Invasive Aspergillosis and Other Filamentous Fungi"],"prefix":"10.1128","volume":"61","author":[{"given":"Amit V.","family":"Desai","sequence":"first","affiliation":[{"name":"Astellas Pharma Global Development, Inc., Northbrook, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4493-4652","authenticated-orcid":false,"given":"Laura L.","family":"Kovanda","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc., Northbrook, Illinois, USA"},{"name":"University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6187-878X","authenticated-orcid":false,"given":"William W.","family":"Hope","sequence":"additional","affiliation":[{"name":"University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Andes","sequence":"additional","affiliation":[{"name":"University of Wisconsin, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6736-4149","authenticated-orcid":false,"given":"Johan W.","family":"Mouton","sequence":"additional","affiliation":[{"name":"Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna L.","family":"Kowalski","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc., Northbrook, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Townsend","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc., Northbrook, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salim","family":"Mujais","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc., Northbrook, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L.","family":"Bonate","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc., Northbrook, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40588-015-0015-1"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.2165\/11596540-000000000-00000"},{"key":"e_1_3_3_4_2","unstructured":"Astellas Pharma Inc. US. 2015. CRESEMBA (isavuconazonium sulfate) prescribing information. http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2015\/207500Orig1s000lbl.pdf."},{"key":"e_1_3_3_5_2","unstructured":"European Medicines Agency. 2015. Cresemba (isavuconazole). http:\/\/www.ema.europa.eu\/ema\/index.jsp?curl=pages\/medicines\/human\/medicines\/002734\/human_med_001907.jsp&mid=WC0b01ac058001d124. 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Clinical outcomes by minimum inhibitory concentrations of baseline Aspergillus pathogens from isavuconazole phase 3 SECURE and VITAL studies, poster EP016. Abstr 25th Eur Congr Clin Microbiol Infect Dis, Copenhagen, Denmark, 25 to 28 April 2015."},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw127"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020191"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1086\/508774"},{"key":"e_1_3_3_18_2","volume-title":"Abstr 54th Intersci Conf Antimicrob Agents Chemother","author":"Box H","year":"2014","unstructured":"Box H GregsonL LivermoreJL FeltonTW WhalleyS GoodwinJ McEnteeL JohnsonA HopeW. 2014. Pharmacodynamics (PD) of isavuconazole (ISA) for invasive pulmonary aspergillosis (IPA), poster A-698. Abstr 54th Intersci Conf Antimicrob Agents Chemother, Washington, DC."},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw098"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01355-13"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02665-15"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04907-14"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12281-015-0226-1"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx029"},{"key":"e_1_3_3_25_2","unstructured":"R project for statistical computing. 2015. R version 3.17. https:\/\/www.r-project.org\/\n."},{"key":"e_1_3_3_26_2","unstructured":"Arundrup\nMC Cuenca-EstrellaM Lass-Fl\u00f6rlC HopeW HowardSJ and the Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID EUCAST. 2015. EUCAST definitive document EDef 9.2: method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for conidia forming moulds. http:\/\/www.eucast.org\/fileadmin\/src\/media\/PDFs\/EUCAST_files\/AFST\/Files\/EUCAST-AFST_EDEF_9_2_Mould_testing_20140815.pdf. Accessed 23 February 2017."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01034-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01034-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:49:18Z","timestamp":1645476558000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01034-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12]]},"references-count":25,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["10.1128\/AAC.01034-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.01034-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12]]},"assertion":[{"value":"2017-05-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-09-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-11-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01034-17"}}