Species differences in the metabolism and hepatotoxicity of coumarin.
1. Investigations of coumarin metabolism and hepatotoxicity have been reviewed. 2. Species differences in coumarin hepatotoxicity appear to be metabolism-mediated. 3. The rat, in which it is markedly hepatotoxic, primarily metabolises coumarin via 3-hydroxylation and cleavage of the heterocyclic ring. 4. Coumarin is less toxic in the baboon, gerbil and certain strains of mice, which resemble man in their extensive formation of the 7-hydroxy metabolite. 5. Liver toxicity in patients receiving relatively high daily doses of coumarin is very rare. 6. Recent studies indicate that coumarin 3,4-epoxide is the metabolic intermediate responsible for hepatotoxicity in the rat.
Fentem
J H
JH
FRAME, Nottingham, U.K.
Fry
J R
JR
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D003374:Coumarins / Q000378:metabolism* / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D008107:Liver Diseases / Q000378:metabolism*; D013045:Species Specificity
D003374:Coumarins; C030123:coumarin