The effects of carbamazepine and valproate on folate metabolism in man

The effect of carbamazepine and valproate treatment on folate metabolism was studied in 11 epileptic patients. The absorption of folic acid and of Pteroyl-gamma-L-glutamyl-gamma-L-glutamyl-L-glutamic acid, a synthetic substrate for intestinal folate deconjugase , was measured prior to and after 2 months of antiepileptic therapy with either carbamazepine (5 cases) or valproate (6 cases). After 2 months' treatment, the area under plasma concentration versus time curve was significantly decreased and t-max (time when maximal plasma concentration is obtained) was significantly prolonged. No inhibition of intestinal folate deconjugation was observed and the liver metabolism of folic acid was found to be unaffected by the treatment. These findings are interpreted as an inhibition of intestinal folic acid absorption caused by the antiepileptic therapy.