Folic acid improves phenytoin pharmacokinetics

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Neuroscience

Background:

• Phenytoin (PHT) therapy for epilepsy is known to decrease serum folate levels in approximately half of patients.
• Folic acid supplementation can prevent folate deficiency but may alter PHT pharmacokinetics.
• Limited data exists on PHT pharmacokinetics with folic acid supplementation in women of childbearing age.

Purpose of the Study:

• To investigate the interdependence of phenytoin (PHT) and folic acid pharmacokinetics in fertile women.
• To assess the effect of folic acid supplementation on serum folate and PHT levels in women of childbearing age.

Main Methods:

• A randomized crossover study involving six fertile women.
• Two treatment arms: Treatment 1 (300 mg sodium PHT daily) and Treatment 2 (300 mg sodium PHT plus 1 mg folic acid daily).
• Daily dietary folate intake was monitored, and serum folate and PHT levels were measured.

Main Results:

• Serum folate levels decreased by 38% during PHT monotherapy (Treatment 1) and increased by 26% with folic acid supplementation (Treatment 2).
• Serum PHT concentrations were similar between treatments, remaining in the low therapeutic range.
• Four out of six subjects achieved PHT steady-state with folic acid supplementation, compared to only one subject without it.

Conclusions:

• Phenytoin therapy necessitates folic acid supplementation in fertile women to maintain adequate serum folate levels.
• Folic acid supplementation appears to improve the achievement of phenytoin steady-state without significantly altering PHT serum concentrations.
• There is a notable interdependence between phenytoin and folic acid metabolism in women of childbearing age.