Inhibition of Drug Precipitation in the Urinary Tract by the Use of Sulfonamide Mixtures. I. Sulfathiazole-Sulfadiazine Mixture. *

Summary

It was observed that N¹-heterocyclic derivatives of sulfanilamide, even if closely related, are soluble in one and the same solution almost to the extent of their separate solubilities. Based on this observation, the toxicity and antibacterial activity of sulfadiazine-sulfathiazole mixtures was investigated. It was found that the acute and chronic toxicity of this drug combination for albino rats is strikingly low if compared with the effect of similar or identical total concentrations of either sulfathiazole or sulfadiazine alone. Evidence derived from chemical analyses and post-mortem examinations pointed to a diminution of intrarenal obstruction from drug precipitate as the chief reason for the low toxicity of the mixture. In vitro antibacterial studies showed that the effectiveness of the mixture corresponded largely to the total concentration of free sulfonamide. On the basis of these observations, the substitution at the bedside of sulfathiazole or sulfadiazine by combinations of these two compounds was suggested, because their application might decrease the danger of renal complications without interfering with the antibacterial efficacy. Clinical trials are in progress.