Changes in hepatic folylpolyglutamate pattern in phenobarbitone-treated rats

Folate deficiency is a common unpleasant secondary effect of anticonvulsant therapy. In order to contribute to the knowledge of biochemical mechanisms leading to this condition, the effects of two i.p. high doses of phenobarbitone administered to the rat (acute treatment) on the distribution of hepatic folate derivatives have been studied. A significant decrease of unsubstituted tetrahydro- and dihydropteroylpentaglutamates and 5,10-methylenetetrahydropentaglutamates was observed. The hypothesis that a lower availability of NADPH, which is utilized for hydroxylation reactions in phenobarbitone metabolism, may limit folate reduction is proposed.