Scholarlink

Background and Objectives <p>ET-26 is a novel etomidate analog with reduced adrenal suppression. This study evaluated its pharmacokinetics (PK), pharmacodynamics (PD), and safety in subjects with mild to moderate renal impairment.</p> Methods <p>In this phase I trial, 24 subjects (normal renal function, mild renal impairment, moderate renal impairment; <i>n</i>&#xa0;=&#xa0;8/group) received a single intravenous bolus ET-26 dose. PK parameters (<i>C</i><sub>max</sub>, AUC<sub>0–∞</sub>, CL), urinary excretion, PD (time to unconsciousness, area under the curve [AUC] of the Bispectral Index [BIS]), and safety were assessed.</p> Results <p>Systemic exposure (AUC<sub>0–∞</sub>) differed by &lt;&#xa0;16% between renal impairment and normal groups (geometric mean ratios: 84.70–86.85%). <i>C</i><sub>max</sub> was ~&#xa0;46% lower in renal impairment groups, but PD responses were comparable. Renal clearance was minimal (CL<sub>r</sub> ≤&#xa0;0.0085&#xa0;L/h; urinary excretion ≤&#xa0;0.02%) with no correlation between estimated glomerular filtration rate (eGFR) and PK parameters. Safety profiles were similar across groups; mild myoclonus (25% per cohort) was the most common adverse event. No renal impairment-specific safety concerns emerged.</p> Conclusion <p>Mild-to-moderate renal impairment minimally affects ET-26 exposure or efficacy due to predominant non-renal elimination. No dosage adjustment is needed for ET-26 0.8&#xa0;mg/kg in these patients. However, patients with severe renal impairment or those receiving dialysis were not studied, and dedicated investigations are required before extrapolating dosing recommendations to these populations. Trial registration: CDE Clinical Trial Registry CTR20233783. Registered on 23 November 2023. <a href="http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml">http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml</a></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Pharmacokinetics, Pharmacodynamics, and Safety of ET-26 in Subjects with Mild to Moderate Renal Impairment

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月15日

查看全文
  • Fan Yang,
  • Chao-Zhuang Shen,
  • Pan-Pan Ye,
  • Wen-Shuo Lv,
  • Li-Ze Li,
  • Jie Shao,
  • Lei Diao,
  • Bo-Wen Ke,
  • Yi Zheng,
  • Xiao-Ran Yang,
  • Wei Zhao

摘要

Background and Objectives

ET-26 is a novel etomidate analog with reduced adrenal suppression. This study evaluated its pharmacokinetics (PK), pharmacodynamics (PD), and safety in subjects with mild to moderate renal impairment.

Methods

In this phase I trial, 24 subjects (normal renal function, mild renal impairment, moderate renal impairment; n = 8/group) received a single intravenous bolus ET-26 dose. PK parameters (Cmax, AUC0–∞, CL), urinary excretion, PD (time to unconsciousness, area under the curve [AUC] of the Bispectral Index [BIS]), and safety were assessed.

Results

Systemic exposure (AUC0–∞) differed by < 16% between renal impairment and normal groups (geometric mean ratios: 84.70–86.85%). Cmax was ~ 46% lower in renal impairment groups, but PD responses were comparable. Renal clearance was minimal (CLr ≤ 0.0085 L/h; urinary excretion ≤ 0.02%) with no correlation between estimated glomerular filtration rate (eGFR) and PK parameters. Safety profiles were similar across groups; mild myoclonus (25% per cohort) was the most common adverse event. No renal impairment-specific safety concerns emerged.

Conclusion

Mild-to-moderate renal impairment minimally affects ET-26 exposure or efficacy due to predominant non-renal elimination. No dosage adjustment is needed for ET-26 0.8 mg/kg in these patients. However, patients with severe renal impairment or those receiving dialysis were not studied, and dedicated investigations are required before extrapolating dosing recommendations to these populations. Trial registration: CDE Clinical Trial Registry CTR20233783. Registered on 23 November 2023. http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml