{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:37:18Z","timestamp":1791308238041,"version":"4.3.1"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2016,8,22]],"date-time":"2016-08-22T00:00:00Z","timestamp":1471824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100007705","name":"Astellas Pharma Global Development, 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":[[2016,9]]},"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 used for the treatment of invasive fungal infections. The objective of this analysis was to develop a population pharmacokinetic (PPK) model to identify covariates that affect isavuconazole pharmacokinetics and to determine the probability of target attainment (PTA) for invasive aspergillosis patients. Data from nine phase 1 studies and one phase 3 clinical trial (SECURE) were pooled to develop the PPK model (NONMEM, version 7.2). Stepwise covariate modeling was performed in Perl-speaks-NONMEM, version 3.7.6. The area under the curve (AUC) at steady state was calculated for 5,000 patients by using Monte Carlo simulations. The PTA using the estimated pharmacodynamic (PD) target value (total AUC\/MIC ratio) estimated from\n            <jats:italic>in vivo<\/jats:italic>\n            PD studies of invasive aspergillosis over a range of MIC values was calculated using simulated patient AUC values. A two-compartment model with a Weibull absorption function and a first-order elimination process adequately described plasma isavuconazole concentrations. The mean estimate for isavuconazole clearance was 2.360 liters\/h (percent coefficient of variation [%CV], 34%), and the mean AUC from 0 to 24 h (AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            ) was \u223c100 mg\u00b7h\/liter. Clearance was approximately 36% lower in Asians than in Caucasians. The PTA calculated over a range of MIC values by use of the nonneutropenic murine efficacy index corresponding to 90% survival indicated that adequate isavuconazole exposures were achieved in &gt;90% of simulated patients to treat infections with MICs up to and including 1 mg\/liter according to European Committee on Antimicrobial Susceptibility Testing methodology and in &gt;90% of simulated patients for infections with MICs up to and including 0.5 mg\/liter according to Clinical and Laboratory Standards Institute methodology. The highest MIC result for PTA was the same for Caucasian and Asian patients.\n          <\/jats:p>","DOI":"10.1128\/aac.02819-15","type":"journal-article","created":{"date-parts":[[2016,7,6]],"date-time":"2016-07-06T02:58:59Z","timestamp":1467773939000},"page":"5483-5491","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":140,"title":["Population Pharmacokinetics of Isavuconazole from Phase 1 and Phase 3 (SECURE) Trials in Adults and Target Attainment in Patients with Invasive Infections Due to Aspergillus and Other Filamentous Fungi"],"prefix":"10.1128","volume":"60","author":[{"given":"Amit","family":"Desai","sequence":"first","affiliation":[{"name":"Astellas Pharma Global Development, Inc., Northbrook, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Kovanda","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc., Northbrook, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Kowalski","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc., Northbrook, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoyang","family":"Lu","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc., Northbrook, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Townsend","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_2_2_2","doi-asserted-by":"publisher","DOI":"10.2165\/11315530-000000000-00000"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/525258"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.2146\/ajhp080325"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-200007000-00006"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.1.279-285.2006"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S51340"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.1.286-293.2006"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01512-07"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1179\/joc.2009.21.3.272"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01217-06"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01216-08"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(02)00892-2"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn431"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02301-13"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl396"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01159-9"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofu052.532"},{"key":"e_1_3_2_19_2","volume-title":"CRESEMBA\u00ae (isavuconazonium sulfate) prescribing information","author":"Astellas Pharma US Inc","year":"2015","unstructured":"Astellas Pharma US Inc. March 2015. CRESEMBA\u00ae (isavuconazonium sulfate) prescribing information. Astellas Pharma US Inc, Northbrook, IL. http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2015\/207500Orig1s000lbl.pdf. Accessed 10 March 2015."},{"key":"e_1_3_2_20_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. Accessed 23 February 2016."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-9485-1"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-75613-4"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.1.13-22.2001"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04907-14"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01193-08"},{"key":"e_1_3_2_26_2","unstructured":"Desai A Yamazaki T Lademacher C Kowalski D Townsend R. 2013. Effect of multiple doses of isavuconazole on the pharmacokinetics of CYP2D6 substrate dextromethorphan in healthy subjects abstr 1799. AAPS Annu Meet Expo San Antonio TX 14 November 2013."},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.0306-5251.2001.01499.x"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00319-09"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2005.07.004"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03752.x"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1177\/1060028015581679"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01355-13"},{"key":"e_1_3_2_33_2","volume-title":"abstr A-698","author":"Box H","year":"2014","unstructured":"Box H, Gregson L, Livermore JL, Felton TW, Whalley S, Goodwin J, McEntee L, Johnson A, Hope WW. 2014. Pharmacodynamics (PD) of isavuconazole (ISA) for invasive pulmonary aspergillosis (IPA), abstr A-698. Abstr 54th Intersci Conf Antimicrob Agents Chemother, Washington, DC, 5 to 9 September 2014."},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00636-13"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01111-13"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aep143"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02819-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02819-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:31:37Z","timestamp":1645475497000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.02819-15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9]]},"references-count":35,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2016,9]]}},"alternative-id":["10.1128\/AAC.02819-15"],"URL":"https:\/\/doi.org\/10.1128\/aac.02819-15","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9]]},"assertion":[{"value":"2015-11-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-06-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-08-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}