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.
Horai
Y
Y
White
P F
PF
Trevor
A J
AJ
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005045:Etomidate / Q000378:metabolism / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors; D010090:Oxidoreductases, O-Demethylating / Q000037:antagonists & inhibitors; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011817:Rabbits
D007093:Imidazoles; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D010090:Oxidoreductases, O-Demethylating; D010089:Oxidoreductases, N-Demethylating; D005045:Etomidate