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This study aimed to develop and validate a physiologically based pharmacokinetic (PBPK) model to predict the effects of hepatic impairment and\n                    <jats:italic>CYP3A4<\/jats:italic>\n                    *22 variants on quetiapine PK. A model was developed using data from healthy individuals administered a single 25 mg dose and validated against 19 independent clinical datasets. Subsequently, the model was adapted to simulate PK in patients with liver cirrhosis (Child\u2010Pugh A, B, and C) and those with\n                    <jats:italic>CYP3A4<\/jats:italic>\n                    *1\/*22 and *22\/*22 genotypes. Simulation results showed a significant increase in systemic exposure and a corresponding decrease in apparent clearance as hepatic impairment worsened or in the presence of\n                    <jats:italic>CYP3A4<\/jats:italic>\n                    *22 alleles. Model\u2010based dose adjustments were proposed and validated, effectively aligning drug exposure levels in specific populations with those observed in healthy controls. In severe cases (Child\u2010Pugh C with\n                    <jats:italic>CYP3A4<\/jats:italic>\n                    *22\/*22), only 5% of the standard dose was required to achieve reference exposure levels. This study demonstrates that PBPK modeling is a valuable tool for optimizing individualized dosing in patients with hepatic impairment or genetic variability. These findings offer clinically relevant insights for safer and more effective quetiapine therapy through evidence\u2010based dose adjustments.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70079","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T02:24:47Z","timestamp":1752719087000},"page":"1719-1731","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Precision Pharmacokinetics of Quetiapine: A Physiologically Based Model Incorporating Liver Cirrhosis and\n                    <i>CYP3A4<\/i>\n                    Polymorphisms"],"prefix":"10.1002","volume":"65","author":[{"given":"Seung\u2010Min","family":"Lee","sequence":"first","affiliation":[{"name":"College of Pharmacy Sunchon National University, Suncheon\u2010si  Jeollanam\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u2010Hun","family":"Jang","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chonnam National University, Buk\u2010gu  Gwangju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7515-0631","authenticated-orcid":false,"given":"Seung\u2010Hyun","family":"Jeong","sequence":"additional","affiliation":[{"name":"College of Pharmacy Sunchon National University, Suncheon\u2010si  Jeollanam\u2010do Republic of Korea"},{"name":"College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences Sunchon National University  Suncheon\u2010si Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.9758\/cpn.2015.13.1.25"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S63779"},{"key":"e_1_2_9_4_1","first-page":"5","article-title":"Receptor pharmacology of neuroleptics: relation to clinical effects","volume":"10","author":"Richelson E","year":"1999","journal-title":"J Clin Psychiatry."},{"key":"e_1_2_9_5_1","unstructured":"DrugBank.Quetiapine [DB01224]. 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