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.