{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T11:42:26Z","timestamp":1760614946497,"version":"build-2065373602"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>To evaluate the pharmacokinetics, pharmacodynamics, and safety of the novel systemic intravenous anesthetic ET-26\u2014an etomidate derivative designed to reduce adrenal suppression\u2014in healthy elderly and non-elderly subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this Phase I, single-center, non-randomized, open-label trial, 16 volunteers were enrolled: eight elderly (\u226565\u00a0years, including \u226575\u00a0years) and eight non-elderly (18\u201364\u00a0years), matched for gender and body weight. Each received a standardized IV infusion of ET-26. Plasma concentrations were measured for plasma protein binding, C<jats:sub>max,<\/jats:sub> and AUC; time to loss of consciousness (LOC) and safety were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In 16 subjects (8 elderly\/8 non-elderly), ET-26 showed higher exposure in the elderly (C<jats:sub>max<\/jats:sub> GMR 198.81%, 90% CI 126.51\u2013312.45) and <jats:inline-formula><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"m1\"><mml:mrow><mml:msub><mml:mtext>AUC<\/mml:mtext><mml:mrow><mml:mn>0<\/mml:mn><mml:mo>\u2212<\/mml:mo><mml:mi>\u221e<\/mml:mi><\/mml:mrow><\/mml:msub><\/mml:mrow><\/mml:math><\/jats:inline-formula> was 23.5% higher (90% CI: 107.6%\u2013141.9%) with comparable pharmacodynamics (median LOC time 1.933\u00a0min). Plasma protein binding remained stable (intergroup difference \u22641.0%). Drug-related TEAEs (37.5%) were mild and self-limiting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Despite elevated systemic exposure in elderly subjects, ET-26 demonstrates comparable efficacy and retains a favorable tolerability profile across age groups, eliminating the need for dose adjustments in elderly populations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration<\/jats:title><jats:p><jats:ext-link>http:\/\/www.chinadrugtrials.org.cn\/clinicaltrials.searchlist.dhtml?keywords=CTR20233784<\/jats:ext-link>, identifier CTR20233784.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1665322","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T11:16:01Z","timestamp":1760613361000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative study of the pharmacokinetics, efficacy and safety of ET-26 in elderly and non-elderly subjects: the results of a phase I clinical trial"],"prefix":"10.3389","volume":"16","author":[{"given":"Fan","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pan-Pan","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Shuo","family":"Lv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Ze","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bao-Zhong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Van Den Anker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo-Wen","family":"Ke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Ran","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.anclin.2019.04.007","article-title":"Geriatric pharmacology: an update","volume":"37","author":"Andres","year":"2019","journal-title":"Anesthesiol. 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