SULFADIAZINE CRYSTALLURIA AND THE INFLUENCE OF pH ON THE THERAPEUTIC EFFICIENCY OF SULFONAMIDES

To the Editor:— In the editorial comment "Prevention of Sulfadiazine Crystalluria" (The Journal, May 29) the question is raised whether alkalization modifies the therapeutic efficiency of sulfadiazine. The relationship between pH and sulfonamide activity has been described in a paper by Fox and Rose entitled "Ionization of Sulfonamides" (Proc. Soc. Exper. Biol. & Med.50:142 [May] 1943). Experimental data were presented showing that antibacterial activity resided in the sulfonamide anion rather than the unionized molecule and that raising the pH increased the activity of the sulfonamides in proportion to the increased ionization that resulted. In addition, the greater potency of sulfadiazine and sulfathiazole as compared to sulfapyridine and sulfanilamide was shown to be a consequence of the fact that at physiologic pH sulfadiazine and sulfathiazole are far more extensively ionized than sulfapyridine and sulfanilamide. Similar results have been reported by Schmelkes and his co-workers (Proc. Soc.