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

Q: What is ET-26 and what was the study trying to assess?

ET-26 is a novel etomidate analog developed to reduce adrenal suppression. The study assessed its pharmacokinetics, pharmacodynamics, and safety in subjects with mild to moderate renal impairment.

Q: How was ET-26 administered and how many participants were included?

A single intravenous bolus ET-26 dose was given in a phase I trial. The study included 24 subjects split into matched cohorts for normal renal function, mild renal impairment, and moderate renal impairment (n=8 per group).

Q: What PK differences were observed between renal impairment and normal renal function?

Systemic exposure measured by AUC0–∞ differed by less than 16% versus the normal group. Cmax was about 46% lower in renal impairment groups, while renal clearance was minimal and urinary excretion was very low, with no correlation between eGFR and PK parameters.

Q: What does the safety and dosing conclusion recommend for patients with mild to moderate renal impairment?

Safety profiles were similar across groups, with mild myoclonus the most common adverse event. Mild-to-moderate renal impairment minimally affected exposure or efficacy, so no dosage adjustment is needed for ET-26 0.8 mg/kg; severe renal impairment and dialysis patients were not studied.

Sep 28, 2026

Uploaded by Callum

ET-26, a novel etomidate analog designed to reduce adrenal suppression, was studied in subjects with mild to moderate renal impairment to determine its pharmacokinetics (PK), pharmacodynamics (PD), and safety after a single intravenous bolus dose. A phase I design enrolled 24 participants, stratified by renal function, to measure exposure (Cmax, AUC0–∞), clearance and urinary excretion, loss of consciousness time, and BIS-AUC. Results showed <16% AUC0–∞ differences versus normal renal function, lower Cmax (~46%), comparable PD responses, minimal renal clearance, and similar safety with mild myoclonus as the most common event, supporting no dose adjustment for 0.8 mg/kg.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Abstract

Background and Objectives

Methods

Results

Conclusion

Study Background

Rationale for Renal Impairment Evaluation

Regulatory Motivation

Drugs in R&D (2025) 25:387–396 [https://doi.org/10.1007/s40268-025-00528-3](https://doi.org/10.1007/s40268-025-00528-3) Pharmacokinetics, Pharmacodynamics, and Safety of ET‑26 in Subjects with Mild to Moderate Renal Impairment Fan Yang1 · Chao‑Zhuang Shen2 · Pan‑Pan Ye1 · Wen‑Shuo Lv1 · Li‑Ze Li3 · Jie Shao3 · Lei Diao3 · Bo‑Wen Ke4 · Yi Zheng1 · Xiao‑Ran Yang3 · Wei Zhao1 Received: 24 August 2025 / Accepted: 3 November 2025 / Published online: 15 December 2025 © The Author(s) 2025 Abstract 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](http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml) | Fan Yang and Chao-Zhuang Shen contributed equally. | | --- | | Yi Zheng, Xiao-Ran Yang and Wei Zhao contributed equally. | * Yi Zheng [yzheng0822@163.com](yzheng0822@163.com) * Xiao-Ran Yang [yangxiaoran@avancpharma.com](yangxiaoran@avancpharma.com) * Wei Zhao [zhao4wei2@hotmail.com](zhao4wei2@hotmail.com) 1 Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China 2 Department of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu, China 3 Avanc Pharmaceutical Co., Ltd, Jinzhou, Liaoning, China 4 Department of Anesthesiology, Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China 1 Background ET-26 is a novel analog of etomidate designed to preserve etomidate's characteristic rapid onset, brief duration of action, and hemodynamic stability, while minimizing adrenal suppression and associated adverse events [1 , 2] . Etomidate has long been valued in clinical anesthesia for its cardiovascular safety profile, especially in hemodynamically unstable patients, but its inhibitory effect on 11β-hydroxylase and subsequent cortisol suppression limits its widespread use, particularly in critically ill or septic patients where adrenal function is critical [3–5] . Preclinical studies demonstrated that ET-26 retains the desirable anesthetic profile of etomidate but with significantly reduced adrenal steroidogenesis inhibition and lower incidence of

FAQs

What is ET-26 and what was the study trying to assess?

ET-26 is a novel etomidate analog developed to reduce adrenal suppression. The study assessed its pharmacokinetics, pharmacodynamics, and safety in subjects with mild to moderate renal impairment.

How was ET-26 administered and how many participants were included?

A single intravenous bolus ET-26 dose was given in a phase I trial. The study included 24 subjects split into matched cohorts for normal renal function, mild renal impairment, and moderate renal impairment (n=8 per group).

What PK differences were observed between renal impairment and normal renal function?

Systemic exposure measured by AUC0–∞ differed by less than 16% versus the normal group. Cmax was about 46% lower in renal impairment groups, while renal clearance was minimal and urinary excretion was very low, with no correlation between eGFR and PK parameters.

What does the safety and dosing conclusion recommend for patients with mild to moderate renal impairment?

Safety profiles were similar across groups, with mild myoclonus the most common adverse event. Mild-to-moderate renal impairment minimally affected exposure or efficacy, so no dosage adjustment is needed for ET-26 0.8 mg/kg; severe renal impairment and dialysis patients were not studied.

Sep 28, 2026

Uploaded by Callum