SCOPARONE O-DEMETHYLASE ASSAY IS NOT USEFUL TO DIFFERENTIATE THE EFFECTS OF MODEL INDUCERS OF CYTOCHROME-P-450 IN RABBIT AND GUINEA-PIG LIVER

Coumarin derivative, scoparone (6,7-dimethoxycoumarin), is regioselect ively O-demethylated into isoscopoletin (I) and scopoletin (S). This o xidation is inversely influenced by cytochrome P-450 inducers in the r at such as 3-methylcholantrene (3-MC) and phenobarbital (PB). The I/S ratio is higher than 1.5 with 3-MC treatment whereas it is lower than 0.5 with PB treatment. With regards to this contrasting effect, it has been suggested that the I/S ratio should be useful to differentiate b etween the effects of these types of inducers. We studied the conseque nces of in vivo PB and 3-MC treatment on scoparone biotransformation i n guinea pig and rabbit. In these two species, at the basal state, sco parone biotransformation was enhanced in comparison to the rat. Moreov er, in these untreated animals, two other metabolites were formed. Aft er 3-MC or PB treatment, scoparone metabolism is, in contrast to the r at, inappropriate to differentiate between the P-450 profile of other animals.