Effect of salicylate on the blood concentration profile and distribution of sulfonamides in rat.

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Abstract
The effect of concomitant administration of salicylate on the pharmacokinetics of 5 sulfonamides antibiotics in rats was studied. Changes in the blood concentration profiles of sulfonamides at the elimination phase due to salicylate treatment were classified into 3 types: I, little change was seen (sulfanilamide); II, the blood concentration was decreased but the disposition rate constant, k.beta., was hardly influenced (sulfadiazine and sulfisoxazole); III, the value of k.beta. decreased (sulfamethoxazole and sulfathiazole). An i.v. administration of salicylate after administration of sulfamethoxazole brought about a sudden decrease in the blood concentration of sulfamethoxazole. The effects of salicylate treatment on the distribution of sulfamethoxazole and sulfadiazine were studied employing a 2-compartment open model. Their distribution to the tissue compartment of the model was increased by the salicylate treatment. The effect of salicylate was interpreted on the basis of a redistributional interaction of sulfonamides with salicylate.