Binding of toxic metabolites of isoniazid by aconiazide

Abstract

Isoniazid, the hydrazide of isonicotinic acid, is widely used in the treatment and prophylaxis of tuberculosis. The toxicity and carcinogenicity of isoniazid have been attributed to the action of its metabolites, hydrazine and acetylhydrazine. Aconiazide, the isonicotinylhydrazone of 2-formylphenoxyacetic acid, has been used in the treatment and prophylaxis of tuberculosis. Aconiazide is hydrolyzed in the body to isoniazid and 2-formylphenoxyacetic acid. 2-Formylphenoxyacetic acid has been shown to bind hydrazine and acetylhydrazine. This binding could explain the lower toxicity of aconiazide and also could provide a reason for postulating its lack of carcinogenicity.