E161111 is an ultra-short-acting etomidate analogue with stable haemodynamics that elicits only slight adrenocortical suppression in rats

PeerJ

article

Bin Wang¹  Deying Gong²  Yi Kang²  Jin Liu²  Jun Yang²  Wen-sheng Zhang² 

[1] Department of Anesthesiology, People’s Hospital of Guizhou Province;Laboratory of Anaesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University;National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University

关键词: Etomidate analogue;    Soft drug;    Adrenocortical suppression;    Ultra-short-acting;    Continuous infusion;    Stable haemodynamics;   

DOI  :  10.7717/peerj.13492

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Purpose We report on a novel ultra-short-acting etomidate analogue, E161111, which has the same primary metabolite as etomidate. Methods The metabolic rate of E161111 was determined in rat plasma and liver homogenate. Rats were infused for 30 or 60 min to maintain light sedation at Richmond Agitation-Sedation Scale (RASS) for −2 to 0 score. Mean arterial pressure (MAP) was monitored during 30 min infusion. The serum corticosterone was determined during and 3 h after infusion as a measure of adrenocortical function. Results E161111 was not detected in rat plasma at 1 min (t1/2 = 6.69 ± 0.07 s) and in rat liver homogenates at 5 min (t1/2 = 10.20 ± 3.76 s); its main metabolic product was etomidate acid. The recovery time from loss of righting reflex (LORR) was 4.3 ± 1.5 min after 1-h infusion of E161111. During 30 min infusion, E161111 did not cause MAP changes. The stimulated serum corticosterone levels after 1-h infusion of E161111 were significantly higher than that after 1-h infusion of etomidate at all time points tested for the 3 h study. Conclusions E161111 was metabolised rapidly, the metabolites were same as etomidate, and the recovery time after 1-h infusion was short. It elicited haemodynamic stability and milder suppression of corticosterone than that elicited by etomidate.

【 授权许可】

CC BY