PHARMACOKINETICS OF SACCHARIN IN THE RAT - RENAL CLEARANCE INVIVO AND IN THE ISOLATED PERFUSED KIDNEY

  • 1 January 1980
    • journal article
    • research article
    • Vol. 8  (2) , 64-67
Abstract
Saccharin [SN] has been implicated as a potential urinary bladder carcinogen as a result of studies conducted in the rat. SN is not metabolized and is rapidly eliminated in rat urine. Factors that affect renal excretion, i.e., protein binding, glomerular filtration rate (GFR), and tubular secretion, would thus be important in determining SN clearance. The renal clearance of SN in the ureter-cannulated rat and in the isolated perfused rat kidney (IPK) were studied after the administration of SN in doses of 0.02, 1, or 100 mg/kg. Binding of SN 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. SN clearance was consistently higher than the GFR, supporting involvement of tubular secretion in the renal elimination of SN. 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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