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Performing clinical studies in such populations has ethical and practical issues. Using predictive physiologically\u2010based pharmacokinetic (PBPK) models in the evaluation of the PK of alectinib, ruxolitinib, and panobinostat exposures in the presence of cancer, RIP, and HIP can help in using optimal doses with lower toxicity in these populations. Verified PBPK models were customized under scrutiny to account for the pathophysiological changes induced in these diseases. The PBPK model\u2010predicted plasma exposures in patients with different health conditions within average 2\u2010fold error. The PBPK model predicted an area under the curve ratio (AUCR) of 1, and 1.8, for ruxolitinib and panobinostat, respectively, in the presence of severe RIP. On the other hand, the severe HIP was associated with AUCR of 1.4, 2.9, and 1.8 for alectinib, ruxolitinib, and panobinostat, respectively, in agreement with the observed AUCR. 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More work is needed to quantify other pathophysiological changes induced by simultaneous affliction by cancer and RIP or HIP.<\/jats:p>","DOI":"10.1002\/bdd.2282","type":"journal-article","created":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T05:56:21Z","timestamp":1619502981000},"page":"263-284","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Physiologically\u2010based pharmacokinetic model for alectinib, ruxolitinib, and panobinostat in the presence of cancer, renal impairment, and hepatic impairment"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0640-8085","authenticated-orcid":false,"given":"Mo'tasem M.","family":"Alsmadi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology Faculty of Pharmacy Jordan University of Science and Technology  Irbid Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour 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