The pharmacokinetics of saccharin in man.

1. After intravenous administration of the non-nutritive sweetener, saccharin (10 mg/kg), to normal volunteers; the plasma concentration--time curve fitted a two-compartment open model with a terminal half-life of 70 min. Renal clearance was high and the dose was recovered quantitatively in the urine. The elimination rate and clearance were decreased significantly by concurrent probenecid administration. 2. After oral administration (2 g) more complex and variable plasma concentration--time curves were obtained and these were reflected in the urinary excretion of saccharin. The fraction absorbed was about 0.85 as determined by the recovery in urine and the area under the plasma concentration--time curves. 3. No indication of saturation of renal elimination was found after oral or intravenous doses that were many times the average daily intake.

Pharmacokinetics of saccharin in the rat. Renal clearance in vivo and in the isolated perfused kidney.

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.

Subacute toxicity studies with sodium saccharin and two hydrolytic derivatives.

The subacute toxicity of sodium saccharin and 2 hydrolytic derivatives, o-sulfamoylbenzoic acid (Compound I) and ammonium o-carboxybenzene sulfonate (Compound II) was evaluated by feeding each of the compounds alone at a dietary level of 20 000 ppm to both beagle dogs and albino rats. Additionally, groups of dogs and rats were fed combinations of the 3 materials at levels up to 20 000 ppm (2000 ppm sodium saccharin, 9000 ppm of both Compound I and II). Dogs were maintained on the test diets for 16 weeks, rats for 13 weeks. No signs of a pharmacotoxic response to the test materials were observed. Parameters determined for treated animals, including growth, food consumption, hematologic profiles, clinical blood chemistry studies, urinalyses, organ weight and ratio data, and both gross and microscopic pathologic evaluation, were not significantly different from control values. From these findings, it is suggested that there is little toxicologic hazard associated with ingestion of the 2 hydrolytic derivatives of sodium saccharin.