The effect of etomidate on rabbit liver microsomal drug metabolism in vitro

Etomidate, an imidazole-containing anesthetic agent, is shown to be a reversible inhibitor of rabbit liver microsomal enzymes in vitro. Inhibition of aniline hydroxylation by etomidate follows competitive kinetics, while inhibition of microsomal N-demethylase and O-demethylase activities is of the mixed type. The concentrations of etomidate required to cause 50% inhibition of these enzyme activities are in the 7-10 microM range. NADPH-cytochrome c reductase is not inhibited by concentrations of etomidate below 100 microM. Spectrophotometric studies show that the addition of etomidate to liver microsomes results in a type II binding spectrum. We suggest that etomidate binds with high affinity to cytochrome(s) P-450, resulting in the inhibition of liver drug metabolism.