Cognitive-motor function in 51 children with seizures well controlled with phenytoin (PHT) monotherapy was assessed in relation to drug concentration, seizure type, and time of medication at the Departments of Psychiatry and Pharmacology, Auckland University School of Medicine, Australia. Age ranged from 4 to 14 years, and performance was significantly better in older patients. Diagnosis (partial vs generalized epilepsy), PHT concentration levels, and change from trough to peak concentration days had little effect. Fluctuations in PHT as great as 50% had no or minimal effects on performance of tests in low therapeutic doses. 
COMMENT. Maintenance phenytoin monotherapy, at relatively low therapeutic levels, had negligible or no effects on cognitive motor function in a group of children with well controlled seizures. Performance swings resulting from drug absorption and elimination were absent or minimal in this carefully monitored study. The importance of frequent determinations of phenytoin levels during evaluations of neuropsychological function in children is evident from the following report.
In a special article on the “role of therapeutic drug monitoring in pediatric anticonvulsant drug dosing,” Walson PD at Children’s Hospital, Columbus, OH refers to a rapid phenytoin clearance and a first order (linear) rather than saturated kinetics observed in some children found to have unusually low serum drug levels despite doses as high as 18 mg/kg/day . The effects of rate and extent of absorption on the interpretation of phenytoin concentrations and cognitive function are often unappreciated. Various factors can modify phenytoin absorption in children, including the dose and stool frequency. Doses well tolerated in healthy children may become toxic if the patient is constipated. High dose phenytoin loading can affect glucose homeostasis, with possible changes in cognition. The hyperglycemic effect of phenytoin was first demonstrated in the Division of Neurology and Neurochemistry Laboratories at Children’s Memorial Hospital, Chicago.