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Bosutinib is a substrate of P\u2010glycoprotein (P\u2010gp) in\u00a0vitro and is predominantly metabolized by CYP3A4 in humans with minimal urinary excretion. We present our perspective on using physiologically based pharmacokinetic modeling to understand the atypical changes in oral exposure of bosutinib, a CYP3A and P\u2010gp substrate, in hepatic impairment patients.<\/jats:p>","DOI":"10.1002\/psp4.70179","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:38:41Z","timestamp":1768451921000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Physiologically Based Pharmacokinetic Modeling in Patients With Hepatic Impairment: Are Changes in Bosutinib Exposure Profiles Driven by Altered Absorption or Distribution?"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4285-4958","authenticated-orcid":false,"given":"Chieko","family":"Muto","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Pfizer R&amp;D Japan  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah M.","family":"Jones","sequence":"additional","affiliation":[{"name":"Simcyp Division Certara UK Limited  Sheffield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7112-2812","authenticated-orcid":false,"given":"Shinji","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Simcyp Division Certara UK Limited  Sheffield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.2257"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3289"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2125"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425250802691074"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40495-021-00266-5"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-012-1987-7"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12901"},{"key":"e_1_2_8_9_1","unstructured":"US Food and Drug Administration (FDA) \u201cApplication Number: 20334Orig1s000. 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