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Isavuconazonium sulfate is approved for the treatment of invasive aspergillosis and invasive mucormycosis in pediatric and adult populations. In the present analysis, an isavuconazole physiologically-based pharmacokinetic (PBPK) model was built and verified in adult and pediatric populations using the Simcyp\n                    <jats:sup>\u00ae<\/jats:sup>\n                    simulator. The verified pediatric model was then used to predict the magnitude of DDI risk in pediatric populations vs. adult populations. The simulations conducted were designed to match the observed clinical trials conducted in adults but with pediatric equivalent doses based on clinical guidelines. Based on the results of the analysis, isavuconazole DDI risk was similar between pediatric and adult populations. When the isavuconazole perpetrator DDI simulations were compared to adults, there was a trend of larger geometric mean (GM) AUC\n                    <jats:sub>inf<\/jats:sub>\n                    and C\n                    <jats:sub>max<\/jats:sub>\n                    ratios in patients 1 to &lt;\u20093 years old receiving the 15\u00a0mg\/kg dose. The GM AUC\n                    <jats:sub>inf<\/jats:sub>\n                    ratio in this study population ranged from 7 to 36% larger than predicted in the adult population. Based on the results of this analysis and literature reports, it is advisable to show greater caution when considering potential DDI in patients\u2009&lt;\u20093-year-old, especially when receiving larger isavuconazonium sulfate doses. In addition, caution should be used in patients\u2009&lt;\u20093 years-old when considering coadministration of isavuconazole with narrow therapeutic index medications such as digoxin and warfarin or medications with large variability in oral bioavailability such as midazolam.\n                  <\/jats:p>","DOI":"10.1007\/s10928-026-10061-8","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:01:52Z","timestamp":1790078512000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of an isavuconazole physiologically-based pharmacokinetic model for adult and pediatric populations"],"prefix":"10.1007","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1771-3245","authenticated-orcid":false,"given":"Mary P","family":"Choules","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7394-3606","authenticated-orcid":false,"given":"Amit","family":"Desai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4493-4652","authenticated-orcid":false,"given":"Laura Lynn","family":"Kovanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Otsuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7618-725X","authenticated-orcid":false,"given":"Roger J","family":"Br\u00fcggemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L","family":"Bonate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"10061_CR1","unstructured":"Astellas (2023) Cresemba (isavuconazonium sulfate) FDA prescribing information"},{"key":"10061_CR2","unstructured":"Cresemba (isavuconazonium sulfate) https:\/\/www.cresemba.com\/. 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Yukio Otsuka is a stockholder of Astellas Pharma, Inc. R.B. has served as a consultant to Astellas Pharma Inc., F2G, Amplyx, Basilea, Elion Tx, Gilead Sciences, Merck Sharp & Dohme Corp., Mundipharma, Pfizer, Inc., and Pulmocide, and has received unrestricted research grants from Astellas Pharma Inc., Basilea, Elion, Gilead Sciences, Merck Sharp & Dohme Corp., and Pfizer, Inc. All contracts were through Radboudumc, and all payments were invoiced by Radboudumc.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"51"}}