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 me...

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Bibliographic Details
Published inArchives internationales de pharmacodynamie et de thérapie Vol. 221; no. 1; p. 140
Main Authors Meuldermans, W E, Lauwers, W F, Heykants, J J
Format Journal Article
LanguageEnglish
Published Belgium 01.05.1976
Subjects
Animals
Centrifugation
Imidazoles - metabolism
In Vitro Techniques
Kinetics
Liver - metabolism
Liver - ultrastructure
Male
Rats
Subcellular Fractions - enzymology
Subcellular Fractions - metabolism
Time Factors
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Summary:(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.
ISSN:0003-9780