Phenobarbital plasma levels 24 hrs after a loading dose, and drug level variations after intravenous maintenance doses, were studied in 25 newborns with seizures admitted to a neonatal intensive care unit at the Maternity-School Hospital of Vila Nova Cachoeirinha, Sao Paulo, Brazil. With a mean loading dose of 19 mg/kg for both term and pre-term infants and a mean maintenance dose of 4 mg/kg/day, a mean plasma level of 23 mcg/ml was obtained at 24 hrs, and therapeutic levels between 15-40 mcg/ml were sustained at 4, 7, 14 and 21 days. A tendency towards drug accumulation in the first week and lower levels after 7 days requires frequent monitoring and dose adjustments. Seizure control without EEG confirmation was obtained in 64%. Phenytoin iv was required in addition in 7 infants and clonazepam in 5. Side effects were limited to infants with severe neurological impairment. [1]

COMMENT. For newborns and infants < 3 months who require phenytoin, the recommended loading dose is 12-20 mg/kg and the maintenance dose is 2-4 mg/kg/d, with 8-12 hr dosing intervals [2]. Phenytoin levels may be modified by phenobarbital because of an increased metabolism during chronic therapy. Phenytoin elimination half-life varies with age: preterm neonate 75 hr; neonate 21 hr; infant and child 7 h; and adult 24 h.