IMPAIRMENT OF INTESTINAL DECONJUGATION OF DIETARY FOLATE: A Possible Explanation of Megaloblastic Anæmia Associated with Phenytoin Therapy

Abstract

Oral administration of phenytoin (diphenylhydantoin, ' Dilantin ', ' Epanutin ') impaired intestinal absorption of conjugated folate in some healthy volunteers but did not significantly affect the absorption of free folate. Phenytoin inhibited the in-vitro deconjugation of polyglutamic folate by homogenates of human intestinal mucosa. These observations suggest that the mechanism for the folate deficiency and megaloblastic anæmia which may accompany chronic anticonvulsant therapy may be inhibition of an enzyme or enzymes responsible for the intestinal deconjugation of folate sources in the diet.