In-vitro metabolism of etomidate by rat liver fractions.
(R)-(+)-etomidate and (S)-(-)-etomidate were found to be metabolized in-vitro by various rat liver homogenization fractions: the 16,000 g supernatant fraction caused a more intensive metabolic breakdown than the microsomal fraction; the 100,000 g supernatant fraction was only slightly active. The metabolism was somewhat more rapid and more extensive for the (R)-(+)-etomidate than for the (S)-(-)-isomer. For both isomers, a dose-dependence was observed: the smaller the substrate concentration, the smaller the relative amount of unmetabolized drug, and the more the rate of metabolic breakdown after a certain incubation time slowed down. Only minor qualitative differences between the metabolic pathways of the two isomers were observed. The main metabolic pathway for the in-vitro metabolism was the hydrolysis of the ethyl ester. Decarboxylation and oxidative N-dealkylation were also observed.
D000818:Animals; D002498:Centrifugation; D007093:Imidazoles / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051381:Rats; D013347:Subcellular Fractions / Q000201:enzymology / Q000378:metabolism*; D013997:Time Factors
D007093:Imidazoles