The effect of diphenylhydantoin (phenytoin) on the sequential stages of intestinal folate absorption.

The drug diphenylhydantoin (phenytoin) (DPH) is thought to interfere with the bioavailability of dietary folate through an effect on intestinal folate deconjugation and/or monoglutamate folate transport. In order to determine whether DPH inhibition occurs in the sequential steps of folate deconjugation, uptake, or reduction-methylation, the effect of the drug on the intestinal absorption of hexaglutamate folate (PteGlu6), pteroylmonoglutamate folate (PGA), and N-5-methyltetrahydrofolate (CH3FH4) was studied. Folate absorption was directly quantified by the method of triple lumen tube perfusion in 12 subjects serving as their own controls. All 12 received PGA mixed with and without DPH (20 micrograms/ml), while 6 of the 12 subjects received hexaglutamate and 6 received reduced methylated folate with and without added DPH. With this model DPH was shown not to impair significantly folate absorption by any action upon the process of folate deconjugation, absorption, or reduction-methylation. The previously reported association between DPH intake and reduced levels of serum folate remains unexplained by these studies.