Inhibition by diphenylhydantoin of folic acid absorption in man.

The association of folate deficiency and diphenylhydantoin administration is well known but not well understood. We have investigated the effect of diphenylhydantoin on absorption of tritiated pteroylglutamic acid with a triple lumen perfusion system. There was a significant reduction in tritiated folic acid absorption when diphenylhydantoin 20 μ g per ml, was added to the perfusion solution. A similar effect occurred with diphenylhydantoin, 100 μ g per ml. Increasing folic acid concentration from 25 ng per ml to 100 ng per ml did not diminish the inhibitory effect. Inhibition was partially sustained in some subjects for 2 hr. Diphenylhydantoin inhibited water and sodium transport in some subjects; this was a variable finding and did not significantly correlate with changes in folate absorption. Diphenylhydantoin concentration in the intestinal lumen after ingestion of a 100-mg Dilantin tablet exceeded the concentration used in perfusion solutions in this study. Inhibition of folic acid absorption may explain, at least in part, the association of diphenylhydantoin therapy and folate deficiency.