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Abstract:
Children require larger relative doses of antiepileptic drugs than adults, and because of the greater patient-to-patient variability among children, an "average" dose is less likely to be correct for a given child. Newborns with convulsions initially have very slow drug elimination; as a group, they also have the widest range of pharmacokinetic values. After the first week of life, drug eliminating mechanisms mature and drug dosage requirements often increase dramatically. Thus in the first 6 weeks of life, intrapatient variation is a significant problem and frequent dosage changes are usually required. Thereafter a given child's kinetics are fairly stable. Infants 2 to 12 months old have the highest rates of drug clearance and often require relative doses that are 3 to 5 times larger than doses for adults. After infancy, relative dosage requirements progressively decline until adult values are reached by 10 to 15 years of age. Newborns, infants, and children, as well as adults, have nonlinear kinetics for phenytoin. Thus a wide range of apparent half-lives occur in children, depending on the phenytoin concentration and other factors. Because the kinetics of antiepileptic drugs are so highly variable in children, antiepileptic drug concentration measurements are an essential aspect of the contemporary treatment of children with epilepsy.