{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:36:36Z","timestamp":1787567796676,"version":"build-2736575974"},"reference-count":14,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Miricorilant is a novel selective glucocorticoid receptor (GR) modulator with mixed agonist\/antagonist effects at the GR and modest antagonism at the mineralocorticoid receptor that is being developed for the treatment of metabolic dysfunction\u2010associated steatohepatitis. Its overall pharmacokinetic characteristics were assessed, including its disposition (absorption, distribution, metabolism, and elimination [ADME]) and drug\u2013drug interaction (DDI) potential. In vitro, miricorilant (1) demonstrated &gt;99% plasma protein binding in mice, rats, monkeys, and humans, (2) was a modest inhibitor of CYP3A4, CYP2C8, CYP2C9, UGT1A1, and a strong inhibitor of BCRP, (3) was predominantly metabolized by CYP2C19 (\u224894%), and (4) showed no induction potential for CYP1A2 and CYP2B6, but showed a concentration\u2010dependent induction of CYP3A4 (6.5\u2010fold) in 1 out of 3 donors tested. In a tissue distribution study in mice, miricorilant was distributed with high levels of radioactivity present in several tissues, including the liver. In animal and human ADME studies, the majority of total radioactivity was recovered in feces (&gt;78%) versus urine (&lt;5%), suggesting hepatic elimination with minor contribution of renal elimination. In phase 1 clinical studies in healthy subjects, miricorilant showed an approximately dose\u2010proportional increase in systemic exposure in the dose range 100\u2013900\u00a0mg with an elimination half\u2010life of \u224820 h. In clinical DDI studies at the total plasma concentrations evaluated, miricorilant was a strong inhibitor of CYP2C8 and a moderate inhibitor of BCRP with no meaningful inhibition of CYP2C9, CYP3A4, or UGT1A1, and a moderately sensitive substrate of CYP2C19. Miricorilant was safe and well\u2010tolerated in the phase 1 studies.<\/jats:p>","DOI":"10.1002\/jcph.70113","type":"journal-article","created":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T10:06:57Z","timestamp":1758967617000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of the Pharmacokinetics, Disposition, and Metabolism of Miricorilant, a Novel Glucocorticoid Receptor Modulator for the Treatment of Metabolic Dysfunction\u2010Associated Steatohepatitis in Nonclinical and Clinical Studies"],"prefix":"10.1002","volume":"66","author":[{"given":"Hazel J.","family":"Hunt","sequence":"first","affiliation":[{"name":"Corcept Therapeutics Incorporated  Redwood City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsteen M.","family":"Donaldson","sequence":"additional","affiliation":[{"name":"Jade Consultants (Cambridge) Ltd.  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeevan R.","family":"Kunta","sequence":"additional","affiliation":[{"name":"Corcept Therapeutics Incorporated  Redwood City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Custodio","sequence":"additional","affiliation":[{"name":"Corcept Therapeutics Incorporated  Redwood City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-016-2161-x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.02.066"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2015.07.020"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.10.015"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-022-00688-6"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0239393"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.20294"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2012.10.074"},{"issue":"12","key":"e_1_2_10_10_1","first-page":"3925","article-title":"Selective glucocorticoid receptor modulation prevents and reverses non\u2010alcoholic fatty liver disease in male mice","volume":"159","author":"Koorneef LL","year":"2018","journal-title":"Endocrinology"},{"issue":"2","key":"e_1_2_10_11_1","first-page":"E48","article-title":"Miricorilant reduced liver fat and cardiometabolic markers in a phase 1b, open\u2010label dose\u2010finding study in patients with non\u2010alcoholic steatohepatitis (NASH)","volume":"79","author":"Alkhouri N","year":"2024","journal-title":"Hepatology"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100187"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(03)00229-7"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.105.005272"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1731"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70113","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.70113","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70113","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:43:15Z","timestamp":1787564595000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,27]]},"references-count":14,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/jcph.70113"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70113","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,27]]},"assertion":[{"value":"2025-06-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70113"}}