{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:09:51Z","timestamp":1789582191812,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,11,5]],"date-time":"2017-11-05T00:00:00Z","timestamp":1509840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Intercept Pharmaceuticals, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Obeticholic acid (<jats:styled-content style=\"fixed-case\">OCA<\/jats:styled-content>) is a semisynthetic farnesoid X receptor (<jats:styled-content style=\"fixed-case\">FXR<\/jats:styled-content>) agonist, an analogue of chenodeoxycholic acid (<jats:styled-content style=\"fixed-case\">CDCA<\/jats:styled-content>) which is indicated for the treatment of primary biliary cholangitis (<jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content>) in combination with ursodeoxycholic acid (<jats:styled-content style=\"fixed-case\">UDCA<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">OCA<\/jats:styled-content> efficiently inhibits bile acid synthesis and promotes bile acid efflux via activating <jats:styled-content style=\"fixed-case\">FXR<\/jats:styled-content>\u2010mediated mechanisms in a physiologically relevant in\u00a0vitro cell system, Sandwich\u2010cultured Transporter Certified \u2122 human primary hepatocytes (<jats:styled-content style=\"fixed-case\">SCHH<\/jats:styled-content>). The study herein evaluated the effects of <jats:styled-content style=\"fixed-case\">UDCA<\/jats:styled-content> alone or in combination with <jats:styled-content style=\"fixed-case\">OCA<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">SCHH<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">UDCA<\/jats:styled-content> (\u2264100\u00a0\u03bcmol\/L) alone did not inhibit <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>7A1 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>, and thus, no reduction in the endogenous bile acid pool observed. <jats:styled-content style=\"fixed-case\">UDCA<\/jats:styled-content> \u2264100\u00a0\u03bcmol\/L concomitantly administered with 0.1\u00a0\u03bcmol\/L <jats:styled-content style=\"fixed-case\">OCA<\/jats:styled-content> had no effect on bile acid synthesis beyond what was observed with <jats:styled-content style=\"fixed-case\">OCA<\/jats:styled-content> alone. Furthermore, this study evaluated human Caco\u20102 cells (clone C2<jats:styled-content style=\"fixed-case\">BB<\/jats:styled-content>e1) as in\u00a0vitro intestinal models. Glycine conjugate of <jats:styled-content style=\"fixed-case\">OCA<\/jats:styled-content> increased <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels of <jats:styled-content style=\"fixed-case\">FXR<\/jats:styled-content> target genes in Caco\u20102 cells, <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>\u201019, <jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> OST<\/jats:styled-content>\u03b1\/\u03b2, and <jats:styled-content style=\"fixed-case\">IBABP<\/jats:styled-content>, but not <jats:styled-content style=\"fixed-case\">ASBT<\/jats:styled-content>, in a concentration\u2010dependent manner, while glycine conjugate of <jats:styled-content style=\"fixed-case\">UDCA<\/jats:styled-content> had no effect on the expression of these genes. The results suggested that <jats:styled-content style=\"fixed-case\">UDCA<\/jats:styled-content> \u2264100\u00a0\u03bcmol\/L did not activate <jats:styled-content style=\"fixed-case\">FXR<\/jats:styled-content> in human primary hepatocytes or intestinal cell line Caco\u20102. Thus, co\u2010administration of <jats:styled-content style=\"fixed-case\">UDCA<\/jats:styled-content> with <jats:styled-content style=\"fixed-case\">OCA<\/jats:styled-content> did not affect <jats:styled-content style=\"fixed-case\">OCA<\/jats:styled-content>\u2010dependent pharmacological effects.<\/jats:p>","DOI":"10.1002\/prp2.368","type":"journal-article","created":{"date-parts":[[2017,11,6]],"date-time":"2017-11-06T02:52:48Z","timestamp":1509936768000},"source":"Crossref","is-referenced-by-count":31,"title":["Comparative potency of obeticholic acid and natural bile acids on <scp>FXR<\/scp> in hepatic and intestinal in\u00a0vitro cell models"],"prefix":"10.1002","volume":"5","author":[{"given":"Yuanyuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Intercept Pharmaceuticals Inc. San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"LaCerte","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals Inc. San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Kansra","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals Inc. San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Qualyst Transporter Solutions, LLC Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth R.","family":"Brouwer","sequence":"additional","affiliation":[{"name":"Qualyst Transporter Solutions, LLC Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2732-8201","authenticated-orcid":false,"given":"Jeffrey E.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals Inc. 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