Plasma Diphenylhydantoin Levels in Australian Children

Summary: The effects of age, sex, dosage increment and concurrent drug therapy on the correlation between plasma diphenylhydantoin concentration and its dosage have been studied in 125 epileptic children. Sex differences and concurrent intake of other drugs had no effect on the correlation but age did. Children below 11 years of age tended to require higher drug doses (on a body weight basis) than older children or adults to attain a given plasma diphenylhydantoin level. The dosage increases necessary to raise plasma diphenylhydantoin levels from 0–7, μ g/ml varied greatly between children, and tended to be higher in children than in adults. When plasma diphenylhydantoin levels were above 7 μ g/ml a given dosage increment (expressed on a body weight basis) tended to have the same effect on plasma diphenylhydantoin level in both children and adults. The data suggest that prepubertal children can metabolize diphenylhydantoin faster than adults, perhaps because they have less steroidal hormones to compete for a metabolic pathway. However, once diphenylhydantoin metabolism approaches saturation (with plasma drug levels above 7 μ g/ml) the drug ac‐cumulates in all individuals largely in proportion to body weight. These data can be used to assist in determining appropriate diphenylhydantoin doses in children.