The effect of methimazole on thioamide bioactivation and toxicity.
The hepatotoxicity induced by administration of ethionamide and thionicotinamide (TNA) was shown to be decreased by pre-administration of methimazole (MMI). Pre-administration of MMI was also shown to decrease the levels of excretion of TNA S-oxide. This indicates that thioamide S-oxidation, mediated by the flavin-containing mono-oxygenase, may be linked to the initiation of hepatotoxicity induced by these thioamides. SK&F-525-A, the cytochrome P-450 inhibitor, did not affect either thioamide-induced toxicity or levels of excretion of TNA S-oxide; however, the role of the P-450 isoenzymes cannot be totally ruled out.
Ruse
M J
MJ
School of Biochemistry, University of Birmingham, U.K.
Waring
R H
RH
D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005000:Ethionamide / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008713:Methimazole / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000201:enzymology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D009536:Niacinamide; D008713:Methimazole; C070820:thionicotinamide; D003577:Cytochrome P-450 Enzyme System; D011335:Proadifen; D005000:Ethionamide