Nonlinear kinetics of phenytoin in children

The nonlinear kinetics of phenytoin were evaluated in 54 children by measuring phenytoin concentrations at steady state at three or more doses. There was good correlation between phenytoin doses and concentrations when a nonlinear kinetic model was used (r = 0.896). Increasing age was associated with a reduction in the apparent Vmax. The apparent Km was influenced primarily by drug interactions. Phenobarbital increased the Km and Vmax for phenytoin. Carbamazepine reduced both Km and Vmax. Valproic acid reduced the Km. The low Km (less than 2.6 mg per liter) found in 28% of patients makes titration of the phenytoin dose to therapeutic levels difficult.