Abstract
Saccharin is not metabolized and is rapidly eliminated in urine of the rat. Factors that affect renal excretion, i.e., protein binding, glomerular filtration rate (GFR), and tubular secretion, would thus be important in determining saccharin clearance. The renal clearance of saccharin in the ureter-cannulated rat and in the isolated perfused rat kidney (IPK) were studies after the administration of saccharin in doses of 0.02, 1, or 100 mg/kg. Binding of saccharin in rat plasma and perfusate was variable and insensitive to changes in concentration. The mean free fraction was approximately 0.70 in rat plasma and 0.40 in perfusate. Renal clearances were relatively constant, with a mean of 2.2 ml/min in vivo and 1.9 ml/min in the IPK. Saccharin clearance was consistently higher than the GFR, supporting involvement of tubular secretion in the renal elimination of saccharin. Correlation of data from IPK experiments with the data from in vivo experiments substantiate the utility of this preparation for studying the renal excretion of drugs.
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