{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:15:58Z","timestamp":1792808158582,"version":"4.5.0"},"reference-count":19,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The estrogen receptor (ER) is the key therapeutic target for ER\u2010positive (ER+) breast cancer. Novel ER degraders may overcome resistance to available endocrine therapy while providing consistent oral bioavailability. Imlunestrant is a novel, orally bioavailable selective estrogen receptor degrader (SERD) designed to deliver continuous ER target inhibition. A phase 1, open\u2010label, 3\u2010site study was conducted to characterize the pharmacokinetic (PK) profile of imlunestrant in individuals with varying degrees of hepatic impairment based on Child\u2010Pugh and National Cancer Institute classifications. In this study, participants received a single oral dose of imlunestrant at either 200 or 400 mg in the fasted state, and the pharmacokinetics and safety were assessed in individuals with normal hepatic function and those with mild, moderate, or severe hepatic impairment. Based on Child\u2010Pugh classification, there were no significant differences in the exposure profiles of imlunestrant in participants with mild hepatic impairment in comparison to participants with normal hepatic function. In participants with moderate and severe hepatic impairment, there were significant increases in imlunestrant AUC (but not C\n                    <jats:sub>max<\/jats:sub>\n                    ) observed when compared with normal hepatic function (by 120% and 191% for AUC(0\u2010t\n                    <jats:sub>last<\/jats:sub>\n                    ) and 122% and 206% for AUC(0\u2010\u221e), respectively). Most treatment\u2010emergent adverse events (TEAEs) were mild or moderate in severity. Nausea and headache were the only TEAEs reported by more than one participant. Treatment\u2010related adverse events were reported by two participants, one each from the moderate and severe hepatic impairment groups. This data will inform the recommendations for dosing patients with hepatic impairment under treatment with imlunestrant.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70181","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:06:24Z","timestamp":1783055184000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of Pharmacokinetics and Safety of Imlunestrant in Participants with Hepatic Impairment"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2365-5360","authenticated-orcid":false,"given":"Amita","family":"Datta\u2010Mannan","sequence":"first","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"White","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Shanks","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Bracknell Berkshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunice","family":"Yuen","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Bracknell Berkshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen David","family":"Hall","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian Rodriguez","family":"Cruz","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejing Aimee","family":"Wang","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.19323"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2024.0035"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15194689"},{"key":"e_1_2_10_6_1","unstructured":"Inluriyo (imluenstrant) tablets for oral use [package insert]. Food and Drug Administration. Revised 2025. Accessed January 25 2026. doi:https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/218881s000lbl.pdf"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2024.10.006"},{"key":"e_1_2_10_8_1","unstructured":"Datta\u2010MannanA SE YuenE GuoY WangX.Evaluation of the effect of food and gastric pH change on the pharmacokinetics and safety of imlunestrant in healthy volunteers. Poster presented at: American Association of Pharmaceutical Scientists PharmSci 360; 2024."},{"key":"e_1_2_10_9_1","unstructured":"Datta\u2010MannanA SE YuenE Rodriguez CruzV WangX HallS.Pharmacokinetic Drug\u2010Drug Interactions of Imlunestrant in Healthy Female Participants of Nonchildbearing Potential. Poster presented at: American Association of Pharmaceutical Scientists PharmSci 360; 2024."},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1562"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1702"},{"key":"e_1_2_10_12_1","unstructured":"Guidance for industry pharmacokinetics in patients with impaired hepatic function; study design data analysis and impact on dosing and labeling. U.S. Food and Drug Administration. Revised January 31 2025. Accessed August 12 2025."},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02733"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010008\u20100553\u2010z"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12901"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1825"},{"key":"e_1_2_10_17_1","unstructured":"Faslodex (fulvestrant) injection for intramuscular use [package insert]. U.S. Food and Drug Administration. Revised 2021. Accessed August 12 2025. doi:https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2011\/021344s015lbl.pdf"},{"key":"e_1_2_10_18_1","unstructured":"Ibrance (palbociclib) capsules for oral use. U.S. Food and Drug Administration. Revised 2024. Accessed August 12 2025. doi:https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/207103s022lbl.pdf."},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2042"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2410858"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70181","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.70181","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70181","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T04:47:42Z","timestamp":1784954862000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70181"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":19,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/jcph.70181"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70181","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2025-10-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70181"}}