Interaction of phenytoin and folate in the rat.

The interactions between folate and phenytoin were studied in the rat using a model in which constant, nontoxic, and continuously protective levels of phenytoin were maintained. After 10 days of treatment with phenytoin, liver folate concentration was decreased while brain, plasma, and adrenal folate concentrations remained unaffected. Oral folate supplementation (20 mg/kg) increased folate concentrations in all tissues examined in phenytoin-treated animals, but had no effect on phenytoin levels. Folate supplementation did, however, increase the recovery time after maximal electroshock seizures in phenytoin-treated rats, but did not influence phenytoin's ability to protect against tonic hindlimb extension. Oral folate supplementation in animals not treated with phenytoin also significantly increased folate concentrations in all tissues examined except brain.