Abstract
During the past 10 years, better results in the treatment of epilepsy have been obtained through the application of pharmacokinetic data to drug therapy of epilepsy. However, pediatric drug therapy is complicated by the continuous change in body weight and body composition with the growth and development, especially during infancy. Younger children require a higher dose per kilogram of body weight than older children in order to achieve comparable plasma concentrations.
Plasma levels and seizure control were investigated in a prospective randomized study when phenytoin, carbamazepine (CBZ) or sodium valproate (VPA) was given as a single drug to pediatric patients with several types of epileptic seizures. Studies on newly referred, previously untreated children suggest that both partial and generalized tonic-clonic seizures can be prevented by each of the three drugs. No significant differences in clinical efficacy were found among the three drugs, when optimum plasma concentration ranges were maintained with blood level monitoring.
Clonazepam (CZP) may be effective in partial seizures. However, as a wide range of plasma levels was associated with complete freedom from seizures, it was not possible to define a therapeutic range for CZP.
Any patient who receives multiple-drug therapy is at risk to develop a drug-drug interaction. Simultaneous administration of VPA was associated with a raised plasma level of carbamazepine-10, 11-epoxide (CBZ-E), a major metabolite of CBZ, relative to the CBZ dose, whereas the plasma CBZ level remained unaltered. High plasma concentration of CBZ-E may be responsible for side effects in some patients.
Drug-protein binding interactions are another source of side effects. The unbound or protein-free levels of both CBZ and CBZ-E in patients treated with CBZ and VPA were significantly higher than those in patients treated with CBZ alone.
A working knowledge of the pharmacokinetic principles is an important basis for treating children with antiepileptic drugs.
