{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:37:33Z","timestamp":1786977453384,"version":"build-2736575974"},"reference-count":14,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T00:00:00Z","timestamp":1705449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cedirogant (ABBV\u2010157) is an orally bioavailable inverse agonist of retinoic acid\u2010related orphan receptor gamma thymus. Data from 2 Phase 1 studies were used to characterize cedirogant pharmacokinetics and evaluate target engagement. Cedirogant plasma concentrations and ex vivo interleukin 17A (IL\u201017A) concentrations from healthy participants and participants with moderate to severe psoriasis (PsO) were analyzed in a population pharmacokinetic and pharmacodynamic modeling framework to characterize cedirogant pharmacokinetics following single and multiple doses and assess ex vivo IL\u201017A inhibition in relation to cedirogant exposure. Cedirogant population pharmacokinetics were best described by a 2\u2010compartment pharmacokinetic model with delayed absorption and an enzyme turnover compartment to describe cytochrome P450 3A autoinduction. The pharmacokinetics of cedirogant were comparable between healthy participants and participants with PsO. Cedirogant steady\u2010state average and maximum plasma concentrations were predicted to be 7.56 and 11.8\u00a0mg\/L, respectively, for participants with PsO for the 375\u00a0mg once\u2010daily regimen on Day 14. The apparent clearance and apparent volume of distribution for cedirogant were estimated to be 24.5 L\/day and 28.2 L, respectively. A direct maximum inhibition model adequately characterized the exposure\u2010response relationship of cedirogant and ex vivo IL\u201017A inhibition, indicating no temporal delay between exposure and response with a saturable inhibition of IL\u201017A. Model\u2010estimated half\u2010maximal inhibitory concentration and maximum inhibition values for cedirogant inhibition of ex vivo IL\u201017A were 0.56\u00a0mg\/L and 0.76, respectively. The established relationship between cedirogant exposure and biomarker effect supported dose selection for the Phase 2 dose\u2010ranging study in patients with PsO.<\/jats:p>","DOI":"10.1002\/cpdd.1377","type":"journal-article","created":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T13:11:10Z","timestamp":1705497070000},"page":"474-484","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cedirogant Population Pharmacokinetics and Pharmacodynamic Analyses of Interleukin\u201017A Inhibition in Two Phase 1 Studies in Healthy Participants and Participants with Moderate to Severe Psoriasis"],"prefix":"10.1002","volume":"13","author":[{"given":"Corinna S.","family":"Maier","sequence":"first","affiliation":[{"name":"Clinical Pharmacology AbbVie  Ludwigshafen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doerthe","family":"Eckert","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie  Ludwigshafen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Stephen","family":"Laroux","sequence":"additional","affiliation":[{"name":"Precision Medicine Immunology AbbVie Inc.  Worcester MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinjal M.","family":"Hew","sequence":"additional","affiliation":[{"name":"Precision Medicine Immunology AbbVie Inc.  South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A.","family":"Suleiman","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie  Ludwigshafen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Inc.  North Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed\u2010Eslam F.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Inc.  North Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199503023320907"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.03096"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301737"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3707"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.07.035"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2021.1948833"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13682"},{"key":"e_1_2_10_9_1","unstructured":"AbbVie Inc.A Study to Assess Adverse Events and Disease Activity With Cedirogant (ABBV\u2010157) in Adult Participants With Moderate to Severe Psoriasis. ClinicalTrials.gov identifier: NCT05044234. Last updated May 17 2022. Accessed May 17 2022.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05044234"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1999.00090.x"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05792-11"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-019-00759-z"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.06.038"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1314258"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1512711"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1377","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T04:00:34Z","timestamp":1713931234000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.1377"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,17]]},"references-count":14,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1002\/cpdd.1377"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.1377","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,17]]},"assertion":[{"value":"2023-09-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}