PLASMA AND BRAIN LEVELS OF PHENOBARBITAL AND DIPHENYLHYDANTOIN IN KEONATES WITH SEIZURES

Utilizing the EMIT system we have determined phenobarbital and diphenylbydantoin levels in 77 neonates with seizures. In addition, brain tissue was obtained for diphenylhydantoin and phenobarbital levels in ten neonates coming to autopsy. Following intravenous loading doses of 15-20mg/kg of phenobarbital, levels of 19.4 ± 3.4 mg/L were achieved. The volume of distribution of phenobarbital was 0.97 ± 0.20 L/kg and was not influenced by gestational age. Following intravenous loading doses of 15-20 mg/kg of diphenylhydantoin, levels of 14.9 ± 2.8 mgm/L were achieved. The volume of distribution of diphenylhydantoin was 1.19 ± 0.19 L/kg. Maintenance doses of 5 mg/kg/d IV, IM or PO phenobarbital or 5 mg/kg/d IV dlphenylhydantoin resulted in accumulation of each agent in the first seven days of therapy. Although the volume of distribution of both agents is significantly greater in the newborn than the adult, the brain to plasma ratio was significantly less in the newborn. It would appear that therapeutic brain concentrations of phenobarbital and diphenylhydantoin are difficult to achieve even when large loading doses of these agents are used.