Phenobarbital and phenytoin binding profiles were determined in 27 neo
nates. Binding of both drugs decreased compared with that in older sub
jects. In vitro binding of both agents correlated significantly with t
otal protein and albumin concentrations. In vivo binding at 0.5 hours
correlated significantly with birthweight and gestational age. Phenoba
rbital, but not phenytoin, binding decreased when three other therapeu
tic agents were concomitantly administered. Bilirubin concentrations,
free fatty-acid concentrations, and pH values encountered in this popu
lation did not significantly influence binding. An in vitro binding pr
ofile accurately predicted in vivo free fractions (percent drug unboun
d) and plasma concentrations of both drugs.