{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T14:24:08Z","timestamp":1787408648508,"version":"build-2736575974"},"reference-count":33,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"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":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Imlunestrant is a next\u2010generation, oral, selective estrogen receptor degrader approved for treating adults with estrogen receptor\u2010positive, human epidermal growth factor receptor 2\u2010negative,\n                    <jats:italic>ESR1<\/jats:italic>\n                    \u2010mutated advanced\/metastatic breast cancer. Imlunestrant is metabolized partly by cytochrome P450 (CYP)3A4 oxidation and conjugation with glucuronic acid and sulfate; thus, pharmacokinetic and drug\u2013drug interaction (DDI) studies for treatments utilizing similar pathways are essential for clinical development. Three open\u2010label, phase 1 studies enrolled 182 healthy females of nonchildbearing potential to assess the tolerability, safety, and pharmacokinetics of imlunestrant as monotherapy or coadministered with other drugs. Drug concentrations were quantified by validated liquid chromatography\u2013mass spectrometry. Participants tolerated imlunestrant at 200\u2013800\u2010mg doses, alone or with a CYP3A inhibitor (itraconazole), CYP3A inducer (carbamazepine), P\u2010glycoprotein (P\u2010gp) inhibitor (quinidine), and substrates of CYP2C8 (repaglinide), CYP2C19 (omeprazole), CYP2D6 (dextromethorphan), CYP3A (midazolam), P\u2010gp (digoxin), and BCRP (rosuvastatin). Frequent treatment\u2010related adverse events included headache (range, 4%\u201320%), diarrhea (2%\u201320%), and constipation (0%\u201316%). In the presence of imlunestrant, exposures (AUC\n                    <jats:sub>0\u2013\u221e<\/jats:sub>\n                    ) increased for dextromethorphan 1.33\u2010fold (90%\u00a0CI, 1.22\u20131.46), digoxin 1.39\u2010fold (1.22\u20131.59), and rosuvastatin 1.49\u2010fold (1.14\u20131.97). Imlunestrant exposure (AUC\n                    <jats:sub>0\u2013\u221e<\/jats:sub>\n                    ) decreased in combination with quinidine (CYP2D6 inhibitor) 0.87\u2010fold (90% CI, 0.76\u20131.00) and carbamazepine (CYP3A4 inducer) 0.58\u2010fold (0.49\u20130.69), but increased in combination with itraconazole (CYP3A4 inhibitor) 2.11\u2010fold (1.77\u20132.53). Imlunestrant had no DDIs with CYP2C8 (repaglinide), CYP2C19 (omeprazole), and CYP3A4 (midazolam) substrates, or a P\u2010gp inhibitor (quinidine), but weakly inhibited dextromethorphan (CYP2D6 substrate), digoxin (P\u2010gp substrate), and rosuvastatin (BCRP substrate) clearance. Thus, considerations should be taken when imlunestrant is coadministered with strong CYP3A4 inhibitors, strong CYP3A4 inducers, and CYP2D6 and P\u2010gp substrates where small changes in exposure may lead to toxicities.\n                  <\/jats:p>","DOI":"10.1111\/cts.70680","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:34:01Z","timestamp":1786509241000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetic Drug\u2013Drug Interactions of Imlunestrant in Healthy Female Participants of Nonchildbearing Potential"],"prefix":"10.1111","volume":"19","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"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4297-3854","authenticated-orcid":false,"given":"Elaine","family":"Shanks","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Bracknell UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2145-6368","authenticated-orcid":false,"given":"Eunice","family":"Yuen","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Bracknell UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6817-4902","authenticated-orcid":false,"given":"Vivian Rodriguez","family":"Cruz","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9032-9505","authenticated-orcid":false,"given":"Xuejing Aimee","family":"Wang","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0268-309X","authenticated-orcid":false,"given":"Stephen David","family":"Hall","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"INLURIYO (Imlunestrant) [Prescribing Information] (2025) accessed December 2025 https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/218881s000lbl.pdf."},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538\u20107445.AM2021\u20101236"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538\u20107445.SABCS20\u2010OT\u201009\u201003"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02733"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2410858"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201022\u20100305"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2022.40.16_suppl.1032"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.73.7585"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(23)00291\u20107"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1562"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2014.41"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13357"},{"key":"#cr-split#-e_1_2_9_14_1.1","unstructured":"A.Datta\u2010Mannan E.Shanks E.Yuen Y.Guo\u2010Avrutin andX. A.Wang \"Evaluation of the Effect of Food and Gastric pH Change on the Pharmacokinetics and Safety of Imlunestrant in Healthy Volunteers \"Poster T0930\u201002\u201007. Poster presented at: 2024 AAPS PharmSci 360 Congress"},{"key":"#cr-split#-e_1_2_9_14_1.2","unstructured":"Salt Lake City UT October 20-23 2024."},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3332"},{"key":"e_1_2_9_16_1","unstructured":"International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) \u201cICH Harmonised Guideline: Drug Interaction Studies. 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