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E161111 is an ultra-short-acting etomidate analogue with stable haemodynamics that elicits only slight adrenocortical
Bin Wang1,2, Deying Gong2,3, Yi Kang2,3
1Department of Anesthesiology, People's Hospital of Guizhou Province, Guiyang, Guizhou, China.
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.
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