A case of a patient who developed symptomatic
phenytoin-induced
folic acid deficiency is reported.
Folate supplementation of 5 mg/d was followed by a decrease of serum
phenytoin concentration to a subtherapeutic level with a breakthrough seizure. Estimation of
phenytoin's Km-Vmax Michaelis-Menten pharmacokinetic parameters in this patient demonstrated that
folate supplements indeed caused a significant decrease in the Km value. This decrease correlates with a greater affinity of the metabolizing hepatic
enzymes for the
drug, and hence, with the resultant increase in
phenytoin's metabolism and decrease of its serum concentration and anticonvulsive effect. In an era of increasing knowledge of
folate's pivotal role in various diseases, we call attention to this
drug-
vitamin interaction, and to the previously suggested recommendation that
folate supplementation should be initiated whenever
phenytoin therapy commences. Because
folic acid dosages as low as 1 mg/d may perturbate
phenytoin's metabolism, smaller deficiency preventive doses may be the advisable allowance for phenytointreated patients with normal pretreatment
folate levels. This suggestion must be confirmed by a prospective study in a large cohort of patients.