OBSERVATIONS ON THE TOXICOLOGY OF SULFATHIAZOLE AND SOME RELATED COMPOUNDS

¹ From the Division of Pharmacology, The Squibb Institute for Medical Research, New Brunswick, N. J.

The doses of the sodium salts of sulfanilamide, sulfapyridine, sulfathiazole, and certain analogues of sulfathiazole which, after a single subcutaneous injection into albino Swiss mice cause a mortality of 50 per cent, were, in terms of millimols per kilogram body weight, as follows: sulfanilamide, 13.45; sulfapyridine, 3.24; sulfathiazole, 5.18; sulfamethylthiazole, 3.29; sulfaethylthiazole, 0.80; sulfaphenylthiazole, 1.39.

The toxic effects of repeated doses of sulfapyridine, sulfathiazole, and sulfamethylthiazole were compared by feeding each drug mixed with the food in concentrations of 0.5 and 1.0 per cent to groups of growing male and female rats for 50 days. The rate of growth, the effects on the liver, kidneys, spleen, and leukocyte-distribution, as well as the terminal blood-levels were all determined. Concretions and associated damage of the kidneys, an increase in the percentage of neutrophiles in the blood, as well as interference with growth, were all most strikingly present as a result of the administration of sulfamethylthiazole. Only sulfamethylthiazole caused lymphoid atrophy of the spleen in rats. Sulfathiazole caused no change in the distribution of leukocytes. In some mammals, such as the mouse and rabbit, toxic symptoms and accompanying pathological changes are more pronounced after the oral administration of repeated doses of sulfathiazole than after sulfapyridine similarly administered (2, 3, 6).

Additional metabolic experiments in rats indicated that after administration by stomach tube, sulfathiazole and sulfapyridine were equally well absorbed during the 24 hours following a single dose but that much less of the sulfathiazole underwent conjugation. It is probable that free sulfathiazole is removed from the blood more rapidly than free sulfamethylthiazole or free sulfapyridine whereas conjugated drug is probably differently excreted.

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