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

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.

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 (C_max, AUC_0-∞, CL), urinary excretion, PD (time to unconsciousness, area under the curve [AUC] of the Bispectral Index [BIS]), and safety were assessed.

Systemic exposure (AUC_0-∞) differed by < 16% between renal impairment and normal groups (geometric mean ratios: 84.70-86.85%). C_max was ~ 46% lower in renal impairment groups, but PD responses were comparable. Renal clearance was minimal (CL_r ≤ 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.

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.

CDE Clinical Trial Registry CTR20233783. Registered on 23 November 2023. http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml.