Effects of nephrotoxic compounds on active uptake of drugs in isolated renal tubules in rabbits.
The uptake of sulfonamides and phenolsulfonphthalein (PSP) was examined in vitro using isolated renal proximal tubule suspension, and the effects of nephrotoxic compounds on the uptake of sulfamethizole (SMZ) were studied. The uptake of SMZ and PSP was energy dependent and was inhibited competitively by iodopyracet (IP), which is transported actively by the p-aminohippurate mechanism. The uptake of sulfamethoxazole was also reduced by IP but that of sulfanilamide was negligible. The present results correspond well with those of in vitro experiments reported previously. Nephrotoxic compounds, mercuric chloride, neomycin, viomycin and kanamycin, decreased the uptake of SMZ non-competitively. The inhibitory action of the three antibiotics corresponds with in vivo potency, suggesting that this renal tubule preparation may provide a simple method for predicting the nephrotoxicity of drugs.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D066298:In Vitro Techniques; D007612:Kanamycin / Q000633:toxicity; D007668:Kidney / Q000187:drug effects*; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D008627:Mercuric Chloride; D008628:Mercury / Q000633:toxicity; D009355:Neomycin / Q000633:toxicity; D010637:Phenolsulfonphthalein / Q000378:metabolism; D011817:Rabbits; D013419:Sulfamethizole / Q000378:metabolism; D014756:Viomycin / Q000633:toxicity; D010130:p-Aminohippuric Acid / Q000378:metabolism
D013419:Sulfamethizole; D008627:Mercuric Chloride; D007612:Kanamycin; D008628:Mercury; D009355:Neomycin; D010637:Phenolsulfonphthalein; D010130:p-Aminohippuric Acid; D014756:Viomycin