The pharmacokinetics of phenytoin (PHT) before and after administration of 1 and 5 mg of folic acid is reported from the Colleges of Pharmacy and Medicine, University of Iowa, Iowa City and University of Health Sciences/The Chicago Medical School, Chicago, IL. The measured total serum PHT concentration was always greater than the calculated concentration and the days to the steady state concentration were always longer than the number calculated before folic acid was given. All subjects showed decreased serum folic acid following PHT. Since folate is assumed to be a co-factor in PHT metabolism, these results were expected because depletion of the vitamin would result in reduced metabolism of PHT and higher total serum PHT and longer time to reach steady state. When folic acid was added the same results were obtained. The depletion of folic acid had to be corrected first before its role as a co-factor in PHT metabolism could be used. 
COMMENT. The authors suggest that folic acid should be prescribed when phenytoin therapy is initiated.