Safety of a higher loading dose of phenobarbital in the term newborn

The conventional loading dose of phenobarbital for newborn infants with hypoxic-ischemic seizures, 20 mg/kg, often fails to control convulsive activity. To determine the safety of a higher loading dose and to establish the pharmacokinetic parameters of a higher loading dose, ten severely asphyxiated term newborns were given 30 mg/kg of phenobarbital intravenously over 15 minutes. The mean serum concentration of phenobarbital two hours after loading was 30.0 +/- 3.2 micrograms/mL, the apparent volume of distribution was 0.97 +/- 0.18 L/kg, total clearance was 0.08 +/- 0.03 mL/min/kg, and mean serum half-life was 148 +/- 55 hours. The higher loading dose was not associated with any short-term adverse effects on cardiorespiratory function, even in spontaneously breathing infants.