{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:19:35Z","timestamp":1789147175118,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2706100"],"award-info":[{"award-number":["2023YFC2706100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82425054;82273784"],"award-info":[{"award-number":["82425054;82273784"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010040","name":"Taishan Scholar Project of Shandong Province","doi-asserted-by":"publisher","award":["NO.tstp20230660"],"award-info":[{"award-number":["NO.tstp20230660"]}],"id":[{"id":"10.13039\/501100010040","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":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Methoxyethyl etomidate hydrochloride (ET\u201026) is a novel intravenous general anesthetic designed to address the clinical limitations of etomidate. This Phase I clinical trial assessed the pharmacokinetics, pharmacodynamics, drug\u2013drug interaction (DDI) potential, and safety of ET\u201026 in 68 healthy subjects across three sequences, evaluating interactions with rifampin (CYP2C19\/3A4 inducer), fluconazole (CYP2C19\/3A4 inhibitor), and omeprazole\/midazolam. ET\u201026 pharmacokinetic analyses showed that compared with administration of ET\u201026 alone, co\u2010administration of rifampin resulted in a 10% decrease in the geometric mean ratio (GMR) of the AUC\n                    <jats:sub>0\u2010\u221e<\/jats:sub>\n                    for ET\u201026 (GMR 90.0%, 90% CI 85.4%\u201094.8%), while co\u2010administration fluconazole increased the AUC\n                    <jats:sub>0\u2010\u221e<\/jats:sub>\n                    by 18.5% (GMR 118.5%, 90% CI 111.4%\u2010126.2%). ET\u201026 slightly increased the AUC\n                    <jats:sub>0\u2010\u221e<\/jats:sub>\n                    by 18.5% for omeprazole (GMR 118.5%, 90% CI 111.4%\u2010126.1%) and 11.1% for midazolam (GMR 111.1%, 90% CI 104.9%\u2010117.8%). The 90% CI for key parameters largely fell within no\u2010effect boundaries, indicating no clinically significant DDIs. Pharmacodynamic assessments showed consistent sedation profiles across sequences, with mild additive effects with midazolam. Safety evaluations identified treatment\u2010emergent adverse events such as injection site pain and myoclonus, more frequent with fluconazole. No serious adverse events were observed. These findings suggest ET\u201026 exhibits a favorable safety and pharmacokinetic profile with no significant DDIs observed in clinical, supporting its potential as a safer alternative to etomidate for general anesthesia.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70071","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T09:55:06Z","timestamp":1751536506000},"page":"1443-1450","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Methoxyethyl Etomidate Hydrochloride (ET\u201026): A Phase I Clinical Trial Assessing Drug\u2013Drug Interactions in Healthy Subjects"],"prefix":"10.1002","volume":"65","author":[{"given":"Fan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy Institute of Clinical Pharmacology Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan\u2010Pan","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy Institute of Clinical Pharmacology Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Shuo","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy Institute of Clinical Pharmacology Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Ze","family":"Li","sequence":"additional","affiliation":[{"name":"Avanc Pharmaceutical Co., Ltd.  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