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PBPK simulation was applied to predict the potential effect of altered DMET profiles on the PK of oral drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All investigated proteins showed trends for reduced expression in inflamed and non\u2010inflamed CD samples relative to healthy individuals. Significant downregulation (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u20090.05) was observed for CYP3A4, AOX1, NAT1 and several SULTs in inflamed ileum as well as UGT1A10, NAT1, BCRP and several SULTs in inflamed and non\u2010inflamed colon. Inter\u2010individual variability was generally higher in CD, with exceptions, for most targets (up to 146%CV in inflamed ileum and up to 169% in histologically normal colon tissues). Integration of abundance data into a verified PBPK model of CD showed a considerable (\u22652\u2010fold; CD predicted relative to healthy predicted) change in systemic drug exposure for 10 drugs examined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CD inflammation significantly suppresses the expression of intestinal DMETs, which, together with changes in other system parameters, can alter the fate of drugs taken orally in these patients. Virtual patients within a PBPK framework, informed by the measured DMET ranges in the intestine, may serve as a guide for dose adjustment in the absence of dedicated clinical studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70019","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T01:04:33Z","timestamp":1741741473000},"page":"2028-2044","source":"Crossref","is-referenced-by-count":6,"title":["Variability in intestinal drug metabolizing enzymes and transporters in Crohn's disease and potential impact on oral drug absorption"],"prefix":"10.1002","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1892-2452","authenticated-orcid":false,"given":"Sarah","family":"Alrubia","sequence":"first","affiliation":[{"name":"Centre for Applied Pharmacokinetic Research, Division of Pharmacy and Optometry, School of Health Sciences University of Manchester  Manchester UK"},{"name":"Pharmaceutical Chemistry Department, College of Pharmacy King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brahim","family":"Achour","sequence":"additional","affiliation":[{"name":"Centre for Applied Pharmacokinetic Research, Division of Pharmacy and Optometry, School of Health Sciences University of Manchester  Manchester UK"},{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy the University of Rhode Island  Kingston Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zubida M.","family":"Al\u2010Majdoub","sequence":"additional","affiliation":[{"name":"Centre for Applied Pharmacokinetic Research, Division of Pharmacy and Optometry, School of Health Sciences University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amin","family":"Rostami\u2010Hodjegan","sequence":"additional","affiliation":[{"name":"Centre for Applied Pharmacokinetic Research, Division of Pharmacy and Optometry, School of Health Sciences University of Manchester  Manchester UK"},{"name":"Certara Predictive Technologies, Certara Inc.  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