Effects of phenobarbitone and phenytoin on folate catabolism in the rat

The effects of phenobarbitone and phenytoin on the catabolism of oral [2-14C] and [3',5',7,9-3H] folic acid were investigated. Normal rats were found to excrete an excess of 3H-labelled compounds into the urine and 14C-labelled compounds into the faeces. Phenytoin abolished this urinary 3H imbalance and also delayed and prolonged the overall excretion of radioactive material. Phenobarbitone appeared to increase the amounts of urinary scission products in the first 24 hr but over the 0-72 hr period both anticonvulsants decreased folate polyglutamate catabolism. As the anticonvulsants used in these experiments decreased folate catabolism in the rat it is unlikely that the megaloblastic anaemia caused by chronic anticonvulsant therapy is due to induction of the enzymes responsible for folate breakdown in vivo.