Effect of phenytoin on folic acid uptake in isolated intestinal epithelial cells.

The anticonvulsant drug phenytoin was found to inhibit the uptake of folic acid into isolated chick intestinal epithelial cells. At a concentration of 100 micrograms/ml the drug inhibited the cellular accumulation of folic acid by 60%. The efflux of folic acid from preloaded cells was not affected by the drug. The inhibition was observed at an acidic pH of 5.8 and at a neutral pH of 7.4. Both the Na+-dependent and the Na+-independent components of folate uptake were inhibited. Phenytoin had no effect on the uptake of the glucose analog 3-O-methylglucose. Thus it was concluded that the effect of phenytoin on folate uptake was not due to changes in Na+ fluxes, concentration gradients or energy metabolism, and suggested instead a direct effect on the folic acid uptake system.