{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:32:22Z","timestamp":1789590742494,"version":"build-2803163510"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T00:00:00Z","timestamp":1722816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:p>Cedirogant is an inverse agonist of retinoic acid\u2010related orphan receptor gamma thymus developed for the treatment of chronic plaque psoriasis. Cedirogant induces cytochrome P450 (CYP) 3A4 while inhibiting P\u2010glycoprotein (P\u2010gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1, and OATP1B3 <jats:italic>in vitro<\/jats:italic>. Static drug\u2013drug interactions (DDIs) predictions suggested possible clinical induction of CYP3A4, and inhibition of P\u2010gp, BCRP, and OATP1B1, leading to challenges in interpreting DDI studies between cedirogant and substrates of CYP3A, P\u2010gp, BCRP, and OATP1B1\/3. Here the effects of cedirogant on the pharmacokinetics of two statin drugs were investigated in healthy participants. Coproporphyrin\u2010I (CP\u2010I), a selective endogenous OATP1B biomarker, was used to assess the impact of cedirogant on OATP1B. Cedirogant (375\u2009mg once daily) increased rosuvastatin maximum plasma concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) and area under the plasma concentration curve (AUC<jats:sub>tau<\/jats:sub>) by 141% and 55%, respectively when co\u2010administered, whereas atorvastatin <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> increased by 40% with no effect on its AUC<jats:sub>tau<\/jats:sub> compared with administration of rosuvastatin\/atorvastatin alone. Cedirogant did not increase CP\u2010I exposures, indicating no clinical OATP1B inhibition. The increased rosuvastatin exposure and minimal change in atorvastatin exposure with co\u2010administration of cedirogant is attributed to BCRP inhibition and interplay between P\u2010gp\/BCRP inhibition and CYP3A induction, respectively. Correlation analysis with data from two investigational drugs (glecaprevir and flubentylosin) demonstrated that OATP1B1 <jats:italic>R<\/jats:italic>\u2010value of &gt;\u20091.5 and [<jats:italic>C<\/jats:italic><jats:sub>max,<jats:italic>u<\/jats:italic><\/jats:sub>]\/[OATP1B1 IC<jats:sub>50<\/jats:sub>] of &gt;\u20090.1 are associated with &gt;\u20091.25\u2010fold increase in CP\u2010I <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> ratio. This demonstrates the utility of CP\u2010I in disentangling mechanisms underlying a complex DDI involving multiple transporters and enzymes and proposes refined criteria for static OATP1B inhibition predictions.<\/jats:p>","DOI":"10.1002\/cpt.3399","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T23:02:01Z","timestamp":1722898921000},"page":"1334-1342","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Coproporphyrin\u2010I as a Selective OATP1B Biomarker Can Be Used to Delineate the Mechanisms of Complex Drug\u2013Drug Interactions: Cedirogant Case Study"],"prefix":"10.1002","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4889-8385","authenticated-orcid":false,"given":"Ryota","family":"Kikuchi","sequence":"first","affiliation":[{"name":"Quantitative, Translational and ADME Sciences AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8986-2189","authenticated-orcid":false,"given":"Yuli","family":"Qian","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Badawi","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7997-8444","authenticated-orcid":false,"given":"John P.","family":"Savaryn","sequence":"additional","affiliation":[{"name":"Quantitative, Translational and ADME Sciences AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2682-7860","authenticated-orcid":false,"given":"Shashikanth","family":"Gannu","sequence":"additional","affiliation":[{"name":"Quantitative, Translational and ADME Sciences AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Eldred","sequence":"additional","affiliation":[{"name":"Immunology Development AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7151-0292","authenticated-orcid":false,"given":"Shuai","family":"Hao","sequence":"additional","affiliation":[{"name":"Discovery and Exploratory Statistics AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9261-1583","authenticated-orcid":false,"given":"Ahmed Hamed","family":"Salem","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Inc.  North Chicago Illinois USA"},{"name":"Clinical Pharmacy Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4444-1230","authenticated-orcid":false,"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4926-1570","authenticated-orcid":false,"given":"Cheri E.","family":"Klein","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Inc.  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