Frontiers in pharmacology · 2025
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.
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Yang Fan, Sun Jing, Ye Pan-Pan, Lv Wen-Shuo, Li Li-Ze, Zhao Bao-Zhong, Van Den Anker John, Zheng Yi, Ke Bo-Wen, Yang Xiao-Ran, Zhao Wei
Аннотация
AIM: To evaluate the pharmacokinetics, pharmacodynamics, and safety of the novel systemic intravenous anesthetic ET-26-an etomidate derivative designed to reduce adrenal suppression-in healthy elderly and non-elderly subjects.
METHODS: In this Phase I, single-center, non-randomized, open-label trial, 16 volunteers were enrolled: eight elderly (≥65 years, including ≥75 years) and eight non-elderly (18-64 years), matched for gender and body weight. Each received a standardized IV infusion of ET-26. Plasma concentrations were measured for plasma protein binding, Cmax, and AUC; time to loss of consciousness (LOC) and safety were assessed.
RESULTS: In 16 subjects (8 elderly/8 non-elderly), ET-26 showed higher exposure in the elderly (Cmax GMR 198.81%, 90% CI 126.51-312.45) and AUC 0 - ∞ was 23.5% higher (90% CI: 107.6%-141.9%) with comparable pharmacodynamics (median LOC time 1.933 min). Plasma protein binding remained stable (intergroup difference ≤1.0%). Drug-related TEAEs (37.5%) were mild and self-limiting.
CONCLUSION: 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.
CLINICAL TRIAL REGISTRATION: http://www.chinadrugtrials.org.cn/clinicaltrials.searchlist.dhtml?keywords=CTR20233784, identifier CTR20233784.
METHODS: In this Phase I, single-center, non-randomized, open-label trial, 16 volunteers were enrolled: eight elderly (≥65 years, including ≥75 years) and eight non-elderly (18-64 years), matched for gender and body weight. Each received a standardized IV infusion of ET-26. Plasma concentrations were measured for plasma protein binding, Cmax, and AUC; time to loss of consciousness (LOC) and safety were assessed.
RESULTS: In 16 subjects (8 elderly/8 non-elderly), ET-26 showed higher exposure in the elderly (Cmax GMR 198.81%, 90% CI 126.51-312.45) and AUC 0 - ∞ was 23.5% higher (90% CI: 107.6%-141.9%) with comparable pharmacodynamics (median LOC time 1.933 min). Plasma protein binding remained stable (intergroup difference ≤1.0%). Drug-related TEAEs (37.5%) were mild and self-limiting.
CONCLUSION: 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.
CLINICAL TRIAL REGISTRATION: http://www.chinadrugtrials.org.cn/clinicaltrials.searchlist.dhtml?keywords=CTR20233784, identifier CTR20233784.