Studies on the Transport Mechanism of Sulfonamides in the Renal Tubules

Abstract

I. Clearance analysis of sulfonamides tranport mechanism in the kidney. (i) Three sulfonamides with Fdifferent values of clearance .(sulfadimethoxine, sulfathiazole, sulfamethizole) and thiosulfate were administeredd orally and intravenously to healthy adults and patients with renal diseases respectively. The sulfonamides/thiosulfate clearance ratios were usually smaller than 1.0. As the value of thiosulfate clearance decreased to smaller than about 50, the ratios tended to increase, and especially the clearane ratio of sulfamethizole was larger than 1.0 in a few uses. The clearance values of acetylated sulfonamides were higher than those of free forms. It was indicated that both free and acetylated form of the sulfonamides were secreted and reabsorbed in the renal tubules. (ii) The sulfonamides (sulfadimethoxine, sulfathiazole) and inulin were administered intravenously to normal dogs. In this experiment, the sulfonamides/inulin clearance ratios were found to increase, when either tubular load of the sulfonamides or urinary pH was elevated, and especially the ratio of sulfathizole approached near 1.0. It was concluded that the sulfonarides were secreted and reabsorbed in the renal tubules in dogs too, considering that those drugs are partially bound to serum protein. II. Stopflow analysis of sulfonamides transport mechanism in the kidney. In an attempt to clarify the transport mechanism of sulfonamides (sulfadimethoxine, sulfathiazole), stopflow analysis was employed in normal dogs. From this study, it was found that both free and acetylated form of the sulfonamides were secreted in the proximal part and reabsorbed in the distal part, and that the secretory site of the sulfonamides was very near the secretory sites of PSP or PAH, and that the reabsorptive site of the sulfonamides was near the reabsorbed site of Na and the secretory site of K. The (U_S/S_S)/(U_IN/S_IN) ratio in the secretory case and the (U_S/S_S) ratio in the reabsorptive case have led us to assume that the active transport mechanism takes part in both secretory and reabsorptive cases of the sulfonamides. Further studies were made to confirm this assumption on the effects of acetate. NaHCO₃, and 2-4 DNP on the sulfonamides transport in the kidney.