Kinetics of placentally transferred phenytoin and its p-hydroxylated metabolites in newborn infants.

1 The kinetics of phenytoin and its main metabolites, unconjugated and conjugated 4-hydroxy-phenytoin were studied in newborn infants of epileptic mothers that were treated with phenytoin during the pregnancy. 2 In two of the infants phenytoin was eliminated by an apparent zero-order process followed by an apparent first-order process. In the other two infants the mode of elimination could not be characterized. 3 The decline of plasma conjugated 4-hydroxy-phenytoin was parallel to that of phenytoin. In contrast, the plasma concentration of unconjugated 4-hydroxy-phenytoin remained grossly constant during the first 3 to 4 days.