DEVELOPMENTAL ASPECTS OF PHENOBARBITAL DOSAGE REQUIREMENTS IN NEWBORN INFANTS FOR SEIZURE CONTROL

Abstract

Phenobarbital (PB) is the most widely used drug to control seizures but specific dosage guidelines are not available in infants of varying gestational ages (GA). The primary objective of this study was to develop the dosage guidelines in newborn infants relative to age to control seizures. Fifty-one patients (27 premature infants: GA 27-38 weeks; 24 term infants) receiving PB, 3-6 mg/kg/d were studied during the first month after birth. Multiple serum concentrations were determined in each patient during extended therapy. Trough serum concentration of PB ranged from 12.5-50.2 μg/ml. PB serum concentrations were within therapeutic range (15-40 μg/ml) in 99 of 114 cases at the maintenance dose of 3.5-4.5 mg/kg/d. The remaining 15 cases were above 35 weeks of GA and required PB doses of 5 mg/kg/d to control seizures. These data suggest that the maintenance dose of PB during the first month after birth should be 3.5-4.5 mg/kg/d in infants < 35 weeks and 4.0-5.0 mg/kg/d in those > 35 weeks GA. Term infants with asphyxia had higher trough serum concentration than those with asphyxia. In six infants, trough serum concentration decreased by 30-50 percent at the same dose during a three weeks period. This suggests that PB serum concentration should be monitored frequently during the developmental period.