Efficacy of primidone for seizure control in neonates and young infants.
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.
Sapin
J I
JI
Department of Pediatrics, St. Christopher's Hospital for Children, Philadelphia, PA 19133.
Riviello
J J
JJ
Grover
W D
WD
D004305:Dose-Response Relationship, Drug; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000188:drug therapy*; D010634:Phenobarbital; D011324:Primidone / Q000009:adverse effects / Q000627:therapeutic use*; D012640:Seizures / Q000188:drug therapy*
D011324:Primidone; D010634:Phenobarbital