{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:25:30Z","timestamp":1789133130648,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Isavuconazole is a broad\u2010spectrum triazole approved for the treatment of invasive aspergillosis or mucormycosis in adults and children aged \u2265\u20091\u2009year. Current prescribing information lacks guidance regarding the co\u2010administration of isavuconazole with anticancer drugs\u2013limited by the availability of clinical drug\u2013drug interaction (DDI) data in the patient population. This study utilized physiologically\u2010based pharmacokinetic (PBPK) modeling to evaluate the DDI risk of isavuconazole compared with other azoles and provide dosing recommendations when co\u2010administered with anticancer drugs (ibrutinib, venetoclax, and midostaurin). PBPK models were developed in the Simcyp simulator using physiochemical properties, in\u00a0vitro, and clinical pharmacokinetic data. The model well\u2010predicted isavuconazole pharmacokinetic changes with cytochrome\u2010P450 3A (CYP3A) modulators (itraconazole and rifampicin), and recovered midazolam DDI with isavuconazole as a CYP3A inhibitor. PBPK models for ibrutinib, venetoclax, and midostaurin were developed and validated by comparing simulated and observed pharmacokinetic parameters with and without the CYP3A inhibitor, ketoconazole. The PBPK model predicted area under the plasma concentration\u2013time curve ratios of 2.1, 1.1, and 2.1 for ibrutinib, venetoclax, and midostaurin, respectively, when co\u2010administered with isavuconazole at clinically relevant doses. The findings suggest that isavuconazole can be safely co\u2010administered following appropriate dose adjustments with ibrutinib (50% of normal dose), venetoclax (50\u2013100% of normal dose), or midostaurin (50% of normal dose). Other azoles, posaconazole and voriconazole, showed larger CYP3A\u2010mediated DDIs and consequently require 3\u20136\u2010fold lower doses of the substrate drugs. In conclusion, this model\u2010informed PK\u2010based dose optimization can enable treatment management in these untested scenarios.<\/jats:p>","DOI":"10.1002\/psp4.70123","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T10:41:04Z","timestamp":1760697664000},"page":"2198-2209","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparative Analysis of Isavuconazole\n                    <scp>DDIs<\/scp>\n                    With Other Azole Antifungal Drugs and\n                    <scp>PBPK<\/scp>\n                    Model\u2010Informed Dosing Recommendations for Anticancer Drugs"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9398-0105","authenticated-orcid":false,"given":"Theunis C.","family":"Goosen","sequence":"first","affiliation":[{"name":"Pharmacokinetics, Dynamics and Metabolism Pfizer Research and Development, Pfizer Inc  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8961-2163","authenticated-orcid":false,"given":"Xiaofeng","family":"Wu","sequence":"additional","affiliation":[{"name":"Pharmacokinetics, Dynamics and Metabolism Pfizer Research and Development, Pfizer Inc  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Lin","sequence":"additional","affiliation":[{"name":"Pharmacokinetics, Dynamics and Metabolism Pfizer Research and Development, Pfizer Inc  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narayan","family":"Cheruvu","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan R.","family":"Raber","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Pfizer Research and Development Pfizer Inc  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Lavinea Novis","family":"de Figueiredo","sequence":"additional","affiliation":[{"name":"Pfizer Inc  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9541-6329","authenticated-orcid":false,"given":"Manthena V. 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