Inhibition of rat liver calciferol 25-hydroxylase activity with anticonvulsant drugs.

Diphenylhydantoin or phenobarbital adminstered for 25 days to Vitamin D-deficient rats inhibited liver calciferol 25-hydroxylase activity. This inhibition was observed with either total homogenate or the microsomal fraction. Eight days following cessation of phenobarbital treatment, liver calciferol 25-hydroxylase activity had returned to control value. Addition of diphenylhydantoin or phenobarbital in vitro to liver homogenate or microsomes isolated from rachitic untreated animals also inhibits the enzymic activity. These data suggest that the impaired conversion of Vitamin D₃ to its 25-hydroxylated metabolite may be the cause of low plasma 25-hydroxycholecalciferol levels in anticonvulsant treated patients.