Drug interaction: diazoxide and diphenylhydantoin

In two children treated for hypoglycemia and convulsions with diazoxide and diphenylhydantoin, therapeutic serum diphenylhydantoin levels were not achieved despite doses of diphenylhydantoin of 17 and 29 mg/kg/day, respectively. After diazoxide was discontinued, serum diphenylhydantoin levels were within the therapeutic range in each patient with doses of 6.6 and 10 mg/kg/day, respectively. Serum diphenylhydantoin fell to undetectable levels within four days after experimental reinitiation of diazoxide administration in one patient. Although the mechanism for the effect of diazoxide on serum concentrations of diphenylhydantoin is uncertain, an increased rate of metabolism of diphenylhydantoin is suggested by our findings. Decreased plasma protein binding of diphenylhydantoin, induced by diazoxide, was observed and may play a role.