Depression of parahydroxylation of diphenylhydantoin by antituberculosis chemotherapy

Abstract

The syndrome of diphenylhydantoin intoxication with nystagmus, ataxia, and drowsiness occurs more frequently in patients who are taking diphenylhydantoin and INH, [Isoniazlde] PAS, [p-amino salicylic acid] or cyclo-serine, or all, than in epileptic patients receiving the same dosage (usually 300 mg daily) of diphenylhydantoin but no antituberculosis drugs. The intoxication is caused by an accumulation of unmetabolized diphenylhydantoin associated with low output of its metabolites indicating depression of diphenylhydantoin metabolism by antltuberculosis and chemotherapy. Isonicotinic acid hydrazide and PAS [p-amino salicylic acid] had to be given in combination to cause diphehylhydantoin accumulation; folic acid stopped that accumulation and increased HPPH [5-(p-hydroxyphenyl)-5-phenylhydantoin] output. A lowered diphenylhydantoin intake provides satisfactory therapeutic blood levels in these patients, eliminating signs of intoxication and at the same time providing adequate prophylaxis against seizures.