Phenobarbital Pharmacokinetics in Neonates

Phenobarbital pharmacokinetics after intravenous injection were studied in 8 neonates with seizures. Subjects ranged in gestational age from 30 to 40 wk. Plasma concentrations of phenobarbital were measured by enzyme-multiplied immunoassay (EMIT). The volume of distribution (Vd) of phenobarbital was 0.97 +/- .15 L/kg which was independent of the dose administered. Vd and gestational age did not correlate. Phenobarbital clearance calculated from average concentrations in patients maintained on phenobarbital for 1 to 4 wks was consistent, with a decrease in t1/2 from 115 hr after 1 wk to 67 hr after 4 wk of therapy. The elimination of phenobarbital decreased at an exponential rate with a t1/2 of 4.6 days. A pharmacokinetic model with an exponentially increasing elimination rate term was used to describe the data. Average concentrations predicted with the use of the model corresponded adequately with experimental results. The increases in clearance observed are thought to be related to rates of turnover of drug-metabolizing enzymes in the neonate.