{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:39:31Z","timestamp":1790645971825,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T00:00:00Z","timestamp":1608076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["T32\u2010HD069038"],"award-info":[{"award-number":["T32\u2010HD069038"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:p>Changes in absorptive capacity and first\u2010pass metabolism in the small intestine affect oral drug bioavailability. Characterization of such changes as a consequence of inflammation is important for developing physiologically\u2010based pharmacokinetic (PBPK) models for inflammatory bowel disease. We sought to elucidate the impact of small intestinal Crohn\u2019s disease (CD) on villous length and CYP3A4 expression in children. Freshly frozen duodenal and terminal ileum (TI) biopsies from 107 children (1\u201319\u00a0years) with and without CD were evaluated for active inflammation. Villous length and CYP3A4 mRNA\/protein expression were compared among regions of active and inactive inflammation in CD and controls. A twofold reduction in villous length was observed in inflamed duodena and ilia of children with CD, but in the absence of regional inflammation, villi in CD were comparable in length to controls. Expression of <jats:italic>CYP3A4<\/jats:italic> mRNA correlated significantly with villous length in the TI (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0003), with a trend observed in the duodenum that did not reach statistical significance. In the presence of active inflammation, a significant decrease in CYP3A protein expression was confirmed in the duodenum, where protein expression also correlated significantly with villous length across diagnoses (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001). Our findings suggest that previous observations of decreased CYP3A4 expression and function in inflamed intestine may not be due solely to downregulation by inflammatory cytokines, but also to villous blunting and subsequent loss of surface area for protein expression. This information is relevant for PBPK model development and could aid with dose adjustment decisions for oral CYP3A4 substrates administered during CD flare (e.g., budesonide).<\/jats:p>","DOI":"10.1111\/cts.12938","type":"journal-article","created":{"date-parts":[[2020,12,5]],"date-time":"2020-12-05T17:51:05Z","timestamp":1607190665000},"page":"729-736","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Effect of Crohn\u2019s Disease on Villous Length and CYP3A4 Expression in the Pediatric Small Intestine"],"prefix":"10.1111","volume":"14","author":[{"given":"Carrie A","family":"Vyhlidal","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Toxicology and Therapeutic Innovation Children\u2019s Mercy Kansas City  Kansas City Missouri USA"},{"name":"Department of Pediatrics University of Missouri - Kansas City School of Medicine  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian D.","family":"Chapron","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Toxicology and Therapeutic Innovation Children\u2019s Mercy Kansas City  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atif","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Missouri - Kansas City School of Medicine  Kansas City Missouri USA"},{"name":"Division of Pathology Children\u2019s Mercy Kansas City  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivekanand","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Pathology UT Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Casini","sequence":"additional","affiliation":[{"name":"NorthShore University Health System  Skokie Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Shakhnovich","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Toxicology and Therapeutic Innovation Children\u2019s Mercy Kansas City  Kansas City Missouri USA"},{"name":"Department of Pediatrics University of Missouri - Kansas City School of Medicine  Kansas City Missouri USA"},{"name":"Division of Pediatric Gastroenterology, Hepatology and Nutrition Children\u2019s Mercy Kansas City  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,16]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1097\/00054725-200405000-00015"},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.12928"},{"key":"e_1_2_11_3_1","first-page":"s39","article-title":"Report: pharmacotherapy for moderate to severe inflammatory bowel disease: evolving strategies","volume":"22","author":"Love B.L.","year":"2016","journal-title":"Am. 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