The effect of regioselective Hepatotoxins on the metabolism of Cimetidine and Metyrapone
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Date
1985
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Obafemi Awolowo University, Ile Ife, Nigeria
Abstract
tetrachloride 24 hr before the administration of either cimetidine or metyrapone. Urine samples
were collected after 24 hr and analyzed for the drugs and their metabolites. All the hepatotoxins
increased the level of cimetidine sulphoxide formation in the male rats. Centrolobular necrotic
agents thioacetamide and carbon tetrachloride inhibited the N-oxidation and keto reduction of
metyrapone in both sexe. and also decreases the sulphoxidation of cimetidine in the female rats
only.
Studies with these hepatotoxic agents indicated. that the S-oxidation of cimetidine n male' rats
are possibly not catalyzed by a cytochrome P-1.50 dependent monooxygenase system but by the
microsomal FFAD--containing monooxygenase system. Sex difference in these reactions was
noted and the possible involvement of cytochrome P-450 female demonstrated.
The keto reduction an%: the -oxidation of metyrapone was demonstrated to be via a cytochrome
P-450 dependent monooxygenase in both sexes. The N-oxidation and keto reduction of metyre one,
the sulphoxida oxidation of cimetidine (female rats only) and the 5-hydroxymethyl-cimetidine
formation were shown to o _e r in the centrolobular region of the liver. The FAD-containing
sulphoxidase was shown to be evenly distributed within the liver lobule.
Description
98p
Keywords
Hepatoxin, Metabolism, Cimetidine, Metyraponeoxidation