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The drug is a strong substrate of cytochrome P450 (CYP) enzymes and efflux transporters. This study aimed to develop a physiologically\u2010based pharmacokinetic (PBPK) model for RIV. It contained three hepatic metabolizing enzyme reactions (CYP3A4, CYP2J2, and CYP\u2010independent) and two active transporter\u2010mediated transfers (P\u2010gp and BCRP transporters). To illustrate the performance of the developed RIV PBPK model on the prediction of drug\u2013drug interactions (DDIs), carbamazepine (CBZ) was selected as a case study due to the high DDI potential. Our study results showed that CBZ significantly reduces the exposure of RIV. The area under the concentration\u2010time curve from zero to infinity (AUC<jats:sub>inf<\/jats:sub>) of RIV was reduced by 35.2% (from 2221.3 to 1438.7\u00a0ng*h\/ml) and by 25.5% (from 2467.3 to 1838.4\u00a0ng*h\/ml) after the first dose and at the steady\u2010state, respectively, whereas the maximum plasma concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) of RIV was reduced by 37.7% (from 266.3 to 166.1\u00a0ng\/ml) and 36.4% (from 282.3 to 179.5\u00a0ng\/ml), respectively. The developed PBPK model of RIV could be paired with PBPK models of other interested perpetrators to predict DDI profiles. Further studies investigating the extent of DDI between CBZ and RIV should be conducted in humans to gain a full understanding of their safety and effects.<\/jats:p>","DOI":"10.1002\/psp4.12844","type":"journal-article","created":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T06:53:34Z","timestamp":1664866414000},"page":"1430-1442","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Application of physiologically\u2010based pharmacokinetic model approach to predict pharmacokinetics and <scp>drug\u2013drug<\/scp> interaction of rivaroxaban: A case study of rivaroxaban and carbamazepine"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0577-4983","authenticated-orcid":false,"given":"Lien Thi","family":"Ngo","sequence":"first","affiliation":[{"name":"College of Pharmacy Chungnam National University  Daejeon 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