Etomidate

Etomidate is a short acting intravenous hypnotic which is rapidly inactivated by enzyme metabolism so that it does not give rise to a hangover effect. It does not release histamine, and has no effect on liver function. In vitro studies have shown etomidate to be an inhibitor of microsomal enzymes. Limited in vivo studies have demonstrated only minimal inhibition of hepatic metabolism.

Adrenal Suppression

Etomidate when used for the introduction of anaesthesia, produces a decrease in plasma cortisol and aldosterone, which remains suppressed for 6-8 hours. These levels usually return to baseline within 24 hours. Etomidate appears to be a specific and reversible inhibitor of the 11-beta-hydroxylation of adrenal steroid synthesis.

Profile in Plasma

After intravenous administration, the time-course of the etomidate plasma levels can be described by a three-compartment model reflecting distribution, metabolism, and elimination processes. Plasma concentrations decrease rapidly for about 30 minutes and then more slowly; traces are still detectable after about 6 hours. Metabolites, chiefly of hydrolysis, are more slowly excreted.

Distribution

Etomidate is approximately 76.5% bound to plasma proteins. Etomidate is rapidly distributed to the brain and other tissues. Its volume of distribution is about 4.5 L/kg.

Metabolism and Elimination

Etomidate is metabolized in the liver. After 24 hours, 75% of the administered dose of etomidate has been eliminated in the urine primarily as metabolites. Only 2% of etomidate is excreted unchanged via the urine. The terminal half-life of about 3 to 5 hours reflects the slow distribution of etomidate from the deep peripheral compartment.

In a reproductive fertility study, results showed no effects on fertility or general pregnancy parameters, and no signs of embryotoxicity or teratogenicity. In standard embryotoxicity and teratology studies, some mortality occurred in the high dose groups (5 mg/kg), however, no embryotoxicity or teratogenicity effects were specifically attributed to the test material. Administration of etomidate during the peri- and post-natal period, resulted in some dose-related maternal mortality and toxicity, and attributed to this, some slight decrease in pup survival in the high dose group (5 mg/kg). No adverse effects were observed on pregnancy rate, litter size, birth weight, or body weight gain, and no offspring abnormalities were noted.