Individualizing phenobarbital dosing in neonates

A method was developed for estimating elimination rate constants for phenobarbital in neonates on the basis of two serum samples drawn at any interval. Phenobarbital serum concentrations were obtained for 16 neonates being treated for fetal asphyxia, intraventricular hemorrhage, narcotic withdrawal, or seizure activity. The mean birth weight was 2.18 kg, mean gestational age was 34.8 weeks, and mean postnatal age was 12.1 days. The first blood sample was drawn two hours after an i.v. loading dose of phenobarbital sodium 7-15 mg/kg; maintenance doses ranging from 1.3 to 7.5 mg/kg/day were given by single i.v. injection. On the third day of therapy, trough concentration was determined; elimination rate constants were calculated using the two concentrations and the total dosage administered. Maintenance doses were adjusted to achieve desired serum concentrations, and predicted concentrations were compared with actual concentrations on the seventh day of therapy. Measured and predicted serum concentrations on day 7 were not significantly different. Only one patient exhibited phenobarbital toxicity. Phenobarbital serum half-life did not show a correlation with either gestational age or postnatal age. This method is clinically useful for individualizing phenobarbital dosing in neonates because it allows for integration of therapeutic drug monitoring with maintenance dosing based on the patient's metabolic capacity for the drug.