Phenytoin elimination in childhood: effect of concentration-dependent kinetics.

The effect of phenytoin (PHT) concentration on the elimination rate of PHT was evaluated in infants, children, and young adults ranging in age from 1 day to 22 years. As PHT concentration increased, the effective half-life (t50%) increased. In eight children, age 7 months to 4.83 years with initial concentrations between 10 to 20 mg per liter, the average t50% (18.6 hours) was approximately 58% as long as the average in adults with comparable concentrations. Whereas the t50% correlated with the initial PHT concentrations, there was no correlation overall between t50% and age, size, or number of other antiepileptic medications taken. The concentration-dependence of the t50% provided the basis for less frequent dosing than one would expect from previous studies of PHT half-life in children with low concentrations.