Abstract
The effect of concomitant administration of salicylate on the pharmacokinetics of five sulfonamides in rats was studied. Changes in the bolld concentration profiles of sulfonamides at the elimination phase due to salicylate treatment were classified into three types : Type I-little change was observed (sulfanilamide) ; Type II-the blood concentration was decreased, but the disposition rate constant, kβ, was hardly influenced (sulfadiazine and sulfisoxazole) ; Type III-the value of kβ decreased (sulfamethoxazole and sulfathiazole). An intravenous 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 two-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.
