Urolithiasis and Renal Pathology After Oral Administration of 2(sulfanilylamino)pyridine (Sulfapyridine)

In the course of an investigation of the pharmacology and toxicology of 2(sulfanilylamino)pyridine, which will be reported elsewhere,∗ we have observed the formation of uroliths in the urinary tract of rats, rabbits, and monkeys fed with this drug, which were found to consist of its acetyl derivative having the formula CH₃CONHC₆H₄SO₂NHC₅H₄N. The appearance of sulfanilamide crystals in the urine of patients has been previously reported by Stewart, Rourke and Allen. 1 †

While concretions have been observed after the administration of a single large dose, the results were more striking after repeated feeding on successive days. The occurrence of urolith formation following the repeated daily administration of 2(sulfanilylamino)pyridine varied greatly in the different species and to some extent even in the same species. Thus uroliths were observed after feeding daily doses of 0.25 g per kilo to monkeys, 10 to 15 g per kilo to rabbits and 5 g per kilo to rats for 10 consecutive days, whereas the phenomenon was not observed in mice or dogs even after the feeding of such excess doses as 20 g per kilo. In a series of 25 monkeys fed doses of 0.25 to 14 g per kilo only one animal (receiving 10 g per kilo) failed to produce uroliths. Individual variation was found to be greater in a series of 30 rabbits and 120 rats, particularly with smaller doses (2 to 5 g per kilo) but the results were quite uniform when large doses (10 to 20 g per kilo) were employed. With small doses, urolith formation was more frequently observed on the right side, while the left ureter remained free of involvement. In contrast to the above results, daily feedings of sulfanilamide over prolonged periods of time produced a similar phenomenon only in 2 rats out of a series of over 300.