Phenytoin/clonazepam interaction.

An interaction between phenytoin (PHT) and clonazepam (CZP) occurred in an epileptic patient, who had been treated with PHT with partial seizure control. The addition of CZP brought about a significant decrease of PHT plasma levels (from 24.8 to 16 micrograms/ml) in spite of increases in the PHT dose. Gradual reduction of CZP, without modifying the PHT dosage, caused significant increases in PHT plasma levels to 42.4 micrograms/ml with signs of intoxication. A review of the literature shows contradictions: some authors state that there is no interaction between the drugs; other authors state either an increase or decrease in PHT plasma levels. These paradoxical results could be explained by the bidirectional effect of these drugs in hepatic enzyme metabolism. The importance of monitoring plasma levels of antiepileptic drugs is emphasized when several medications are required in the treatment of epilepsy.

Plasma levels of diphenylhydantoin and the control of adult epileptic seizures: a Chilean experience.

In a prospective study of 117 adult ambulatory patients, 110 of whom were epileptics treated only with oral diphenylhydantoin (DPH), plasma levels of this drug were determined by gas-liquid chromatography. The average follow-up time was 6 months (range, 3 to 13 months); satisfactory control of seizures was obtained with plasma levels in the 10.2 to 25.8 micrograms/ml range, representing 68% of the patients whose seizures had been controlled. The dosage received by this group was from 4.2 to 6 mg/kg, with an average of 5.1. In general, these results agree with those found in European or North American patients, even though some differences or little clarity in the methodology of other trials make comparison difficult. This similarity of results makes one think that genetic or environmental differences do not alter the response to DPH in our patients, but further studies are necessary in that area. This paper can serve as a basis for the extrapolation of data about DPH coming from other latitudes that have been considered supposedly valid for Latin American epileptic patients.