Methoxyethyl Etomidate Hydrochloride (ET‐26): A Phase I Clinical Trial Assessing Drug–Drug Interactions in Healthy Subjects.
Methoxyethyl etomidate hydrochloride (ET‐26) is a novel intravenous general anesthetic designed to address the clinical limitations of etomidate. This Phase I clinical trial assessed the pharmacokinetics, pharmacodynamics, drug–drug interaction (DDI) potential, and safety of ET‐26 in 68 healthy subj...
| Publicado en: | Journal of Clinical Pharmacology Vol. 65; no. 11; pp. 1443 - 1451 |
|---|---|
| Autores principales: | , , , , , , , , , , , |
| Formato: | clinical trial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Nov2025
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=188898504&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 188898504 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00912700 5WH jtl: Journal of Clinical Pharmacology issn: 00912700 maglogo: Y pubinfo: dt: Nov2025 vid: 65 iid: 11 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 188898504 186332001 188898504 188898504 10.1002/jcph.70071 188898504 ppf: 1443 ppct: 8 formats: tig: atl: Methoxyethyl Etomidate Hydrochloride (ET‐26): A Phase I Clinical Trial Assessing Drug–Drug Interactions in Healthy Subjects. aug: au: Yang, Fan Ye, Pan‐Pan Lv, Wen‐Shuo Li, Li‐Ze Zhao, Bao‐Zhong van denAnker, John Yang, Xin‐Mei Song, Lin‐Lin Yang, Xiao‐Ran Zheng, Yi Ke, Bo‐Wen Zhao, Wei affil: 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 sug: subj: Etomidate Administration and Dosage Drug Interactions Evaluation Etomidate Pharmacokinetics Etomidate Pharmacodynamics Patient Safety Evaluation Human Clinical Trials Adolescence Adult Rifampin Administration and Dosage Fluconazole Administration and Dosage Omeprazole Administration and Dosage Midazolam Administration and Dosage Adverse Drug Event Risk Factors China Descriptive Statistics Confidence Intervals Treatment Related Pain Risk Factors Injection Sites Myoclonus Risk Factors Male Female Body Mass Index ROC Curve Data Analysis Software Funding Source Adolescent: 13-18 years Adult: 19-44 years Male Female ab: Methoxyethyl etomidate hydrochloride (ET‐26) is a novel intravenous general anesthetic designed to address the clinical limitations of etomidate. This Phase I clinical trial assessed the pharmacokinetics, pharmacodynamics, drug–drug interaction (DDI) potential, and safety of ET‐26 in 68 healthy subjects across three sequences, evaluating interactions with rifampin (CYP2C19/3A4 inducer), fluconazole (CYP2C19/3A4 inhibitor), and omeprazole/midazolam. ET‐26 pharmacokinetic analyses showed that compared with administration of ET‐26 alone, co‐administration of rifampin resulted in a 10% decrease in the geometric mean ratio (GMR) of the AUC0‐∞ for ET‐26 (GMR 90.0%, 90% CI 85.4%‐94.8%), while co‐administration fluconazole increased the AUC0‐∞ by 18.5% (GMR 118.5%, 90% CI 111.4%‐126.2%). ET‐26 slightly increased the AUC0‐∞ by 18.5% for omeprazole (GMR 118.5%, 90% CI 111.4%‐126.1%) and 11.1% for midazolam (GMR 111.1%, 90% CI 104.9%‐117.8%). The 90% CI for key parameters largely fell within no‐effect boundaries, indicating no clinically significant DDIs. Pharmacodynamic assessments showed consistent sedation profiles across sequences, with mild additive effects with midazolam. Safety evaluations identified treatment‐emergent adverse events such as injection site pain and myoclonus, more frequent with fluconazole. No serious adverse events were observed. These findings suggest ET‐26 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. pubtype: Academic Journal doctype: clinical trial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|