{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T12:30:51Z","timestamp":1787056251059,"version":"build-2736575974"},"reference-count":57,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Etrasimod is an oral sphingosine\u20101\u2010phosphate receptor modulator approved for moderate\u2010to\u2010severe ulcerative colitis. The impact of CYP2C9 polymorphisms and hepatic impairment on etrasimod exposure remains unclear. This study aimed to characterize their effects and identify clinically relevant dose adjustment strategies in Chinese patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A physiologically based pharmacokinetic model was developed and verified using in vitro metabolism and single\u2010dose, multiple\u2010dose and drug\u2013drug interaction clinical pharmacokinetic data. The validated model was extrapolated to Chinese populations with different CYP2C9 genotypes and hepatic impairment severity to characterize exposure changes and optimize dosing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Most predicted pharmacokinetic parameters are within a twofold error range. At the approved dose of 2\u2009mg once daily, the predicted median steady\u2010state AUC\n                      <jats:sub>0\u201324<\/jats:sub>\n                      and C\n                      <jats:sub>max<\/jats:sub>\n                      were 1976.95\u2009ng\u00b7h\/mL (95% prediction interval [PI]: 975.78\u20134144.29\u2009ng\u00b7h\/mL) and 98.40\u2009ng\/mL (95% PI: 52.9\u2013190.51\u2009ng\/mL) in Caucasian subjects and 1988.82\u2009ng\u00b7h\/mL (95% PI: 814.91\u20134244.10\u2009ng\u00b7h\/mL) and 105.18\u2009ng\/mL (95% PI: 51.30\u2013198.03\u2009ng\/mL) in Chinese subjects, respectively. In Chinese populations, hepatic impairment and CYP2C9 polymorphisms increased etrasimod exposure, with the greatest increase observed in CYP2C9 poor metabolizers with Child\u2013Pugh C hepatic impairment (67% increase in AUC\n                      <jats:sub>ss<\/jats:sub>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CYP2C9 polymorphisms and hepatic impairment increased etrasimod exposure, particularly when combined. Model\u2010based exposure matching supported dose reduction to 1.5\u2009mg once daily for most affected subgroups and to 1\u2009mg once daily for CYP2C9 poor metabolizers with Child\u2013Pugh C hepatic impairment, providing quantitative support for individualized dosing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70777","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T12:14:51Z","timestamp":1787055291000},"source":"Crossref","is-referenced-by-count":0,"title":["Model\u2010informed dose optimization of etrasimod in ulcerative colitis across CYP2C9 genotypes and hepatic impairment"],"prefix":"10.1002","author":[{"given":"Zihan","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmaceutical Sciences Fudan University  Shanghai 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