Neonatal population pharmacokinetics of phenobarbital derived from routine clinical data.

Routine clinical pharmacokinetic (PK) data collected from 59 preterm infants who received phenobarbital were analyzed to estimate population PK parameters. Birth weights ranged from 600 to 3,620 g (mean 1,520 g), and gestational ages ranged from 24 to 42 weeks (mean 31 weeks). Data were analyzed using NONMEM, a computer program designed for population PK analysis. The mean (+/- CV) clearance of phenobarbital was 0.0047 liter/h/kg (+/- 19%) and the mean (+/- CV) volume of distribution (Vd) was 0.96 liter/kg (+/- 16%). The calculated mean serum half-life was 141 h. Clearance was not affected by gestational age, sex, asphyxia, or duration of therapy. Vd was not affected by gestational age or sex but was increased by 13% in the presence of asphyxia (5-min Apgar score less than 5, p less than 0.05).