Search

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.

Tuberculin purified protein derivative labeled with 14C ([14C]PPD) with a biological potency equivalent to the International Standard for tuberculin PPD was used to study the retention of tuberculin PPD in the skin of sensitized and nonsensitized animals. We found that [14C]PPD was almost entirely cleared from the skin test site during the first 18 to 24 h after injection and that when approximately 5% of the initial concentration of [14C]PPD was present in the skin test site, the size of the tuberculin skin reaction in sensitized guinea pigs was at its maximum. Furthermore, the addition of 5 or 50 μg of Tween 80 per ml to a solution of PPD did not change either the rate of clearance of PPD from the skin test sites of sensitized guinea pigs or the size of the tuberculin skin reactions. There was no difference in the rate of clearance of [14C]PPD from the skin test sites between sensitized and nonsensitized guinea pigs and between guinea pigs of different age. However, there was a significant difference in the rate of clearance of [14C]PPD between the guinea pig and the mouse. Finally, the percentage of [14C]PPD retained in the site of injection at 24 h was in the neighborhood of 5% of the initial concentration of the solution of PPD injected. The significance of these phenomena is discussed.