FOLIC-ACID IMPROVES PHENYTOIN PHARMACOKINETICS

Phenytoin (PHT) therapy to control seizures decreases serum folate lev els in half of epileptic patients, thus increasing the risk of folate depletion. Supplementation with folic acid prevents deficiency but als o changes PHT pharmacokinetics. Kinetic monitoring of PHT when folic a cid is provided as a supplement has not been reported in women of chil dbearing age. This study of six fertile women examined the interdepend ence of PHT and folic acid in a randomized crossover study of two trea tments: treatment 1 consisted of 300 mg sodium PHT per day and treatme nt 2 consisted of 300 mg sodium PHT plus 1 mg folic acid per day. Diet ary folic acid intake was calculated daily. During treatment 1, serum folate level decreased 38.0+/-18.6% (mean+/-standard deviation) and se rum PHT concentration was in the low therapeutic range (43.92+/-14.52 mu mol/L). During treatment 2, serum folate level increased 26.0+/-33. 4%, and serum PHT level (39.04+/-14.16 mu mol/L) was similar to that i n treatment 1. Only one subject attained PHT steady state during treat ment 1, but four subjects achieved steady state during treatment 2. Di etary folate intakes during treatments 1 and 2 were not significantly different. This study suggests an interdependence between PHT and foli c acid and supports the observation that fertile women treated with PH T require folic acid supplementation to maintain a normal serum folate level.