Effect of salicylate on the metabolism and urinary excretion of sulfonamides in the rat.

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Abstract
The effect of concomitant administration of salicylate on the acetylation and urinary excretion of sulfonamides (sulfanilamide, sulfamethoxazole, sulfadiazine, sulfisoxazole and sulfathiazole) after i.v. administration to rats was studied. The degree of acetylation of sulfamethoxazole in rat urine was significantly decreased by salicylate treatment, but that of sulfathiazole was increased. The eliminations of sulfamethoxazole and sulfathiazole from rat blood were markedly reduced by the concomitant administration of salicylate. Urine samples were collected at intervals and the rate constant of urinary excretion and that of acetylation were calculated employing the elimination rate constant from rat blood. The decrease in the elimination of sulfamethoxazole on salicylate treatment was explained on the basis of a decrease in the acetylation rate constant. For sulfathiazole, the decrease in the elimination was due to a decrease in the excretion rate constant due to the inhibitory effect of salicylate treatment on the excretion of unchanged sulfathiazole.