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Phenytoin elimination in childhood

Effect of concentration-dependent kinetics

Edward Mallinckrodt Department of Pediatrics, Division of Child Neurology, and the Department of Neurological Surgery and Neurology (Neurology), Washington University school of Medicine Division of Pediatric Neurology, St. Louis Children's Hospital, St. Louis, MO.

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 (t_50%) increased. In eight children, aged 7 months to 4.83 years with initial concentrations between 10 to 20 mg per liter, the average t_50% (18.6 hours) was approximately 58% as long as the average in adults with comparable concentrations. Whereas the t_50% correlated with the initial PHT concentrations, there was no correlation overall between t_50% and age, size, or number of other antiepileptic medications taken. The concentration-dependence of the t_50% provided the basis for less frequent dosing than one would expect from previous studies of PHT half-life in children with low concentrations.

Address correspondence and reprint requests to Dr. Dodson, St. Louis Children's Hospital, 500 S. Kingshighway, P.O. Box 14871, St. Louis, MO 63178.

Accepted for publication June 25, 1979.

This work was supported by grants from the National Foundation-March of Dimes; Public Health Service Research Grant No. RR-36 from the General Clinical Research Center Branch, Division of Research Facilities and Resources, Bethesda, MD, and NIH Mass Spectrometry Resource Grant No. RR-00954. The author is the recipient of NIH Career Academic Development Award No. 1-K07 NS11074.