Primidone can be used for
seizures refractory to standard
antiepileptic drugs. We administered
primidone, 25 mg/kg/day in 3 divided doses, to 10 patients and obtained serum levels of
primidone,
phenobarbital, and phenylethylmalonic
acid at 1, 2, 4, 6, and 8 hours on day 1, alternate days until discharge, and after 6 weeks. Other
antiepileptic drugs were discontinued in 8 of 10 patients with refractory
seizures. Mean
primidone levels were 10.6 +/- 4.4 micrograms/ml by day 3 and remained stable until discharge. Phenylethylmalonic
acid was detected by 6 hours and increased to 11.1 +/- 4.0 micrograms/ml by day 7.
Phenobarbital levels in 3 of 10 patients not previously treated with
phenobarbital ranged from 0.6-3.4 micrograms/ml by day 5. The mean initial
phenobarbital level was 30.1 +/- 10.5 micrograms/ml and had decreased to less than 15 micrograms/ml by day 7. Seizure control occurred within 5 days in 8 of 10 patients and was achieved by day 3 in 6 of 8 patients, coinciding with
primidone levels greater than 10 micrograms/ml. No toxic effects of
primidone were observed. All levels decreased during subsequent examinations suggesting auto-induction of metabolic systems. Our data indicate that seizure control is best correlated with
primidone and phenylethylmalonic
acid levels and unrelated to
phenobarbital levels in this age group.