Diphenylhydantoin Metabolism, Blood Levels, and Toxicity

Abstract

Introduction Diphenylhydantoin is one of the most frequently used anticonvulsants, and it has a relatively low incidence of serious side reactions. The common signs of dose-related toxicity are nystagmus, ataxia, dysarthria, and drowsiness. Diphenylhydantoin must usually be given to adults in amounts of 500 mg or more a day¹ to produce clinical evidence of intoxication. Buchthal et al² reported that mild toxic symptoms and signs were observed with blood levels of 15μg/ml, and severe symptoms and signs have been noted with diphenylhydantoin blood levels of 30μg/ml or more. However, this report does not give a detailed account of the relationship of the specific symptoms and signs of toxicity to diphenylhydantoin blood levels. Along with our studies of toxicity and defects in the metabolism of diphenylhydantoin, detailed data have been obtained relating symptoms and signs of toxicity to blood levels of diphenylhydantoin. The first part of this paper deals