Abstract
Summary
1. In continuation of experimental and clinical studies with mixtures of sulfonamides, the toxicity as well as the absorption and excretion of the combinations sulfadiazme-sulfathiazole, sulfadiazine-sulfa-merazine, and sulfadiazine-sulfathiazole-sul-famerazine were investigated in albino rats.
2. These combinations of partial dosages proved significantly less toxic than any one of their separate constituents in equal or comparable total dosage. The mixture of 3 sulfonamides was less toxic than either combination of 2 drugs.
3. The low toxicity of sulfonamide mixtures was shown to be due to the prevention of renal obstruction, resulting from a pronounced diminution in the intratubular deposition of sulfonamide crystals.
4. Mixtures of sulfonamides were more completely absorbed and excreted than equal amounts of their individual constituents. Blood levels from mixtures were, therefore, distinctly higher than expected on the basis of mathematical computations from the values of single sulfonamides.
5. It was reasoned on the basis of these experimental studies that the use of a mixture containing 3 sulfonamides in human therapy would almost completely eliminate the possibility of concrement formation in the urinary tract at the routine dose level. Hence, it would also obviate the necessity for adjuvant alkali therapy.
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