The Fate of Saccharin Impurities: The Excretion and Metabolism of Toluene-2-sulphonamide in Man and Rat

Abstract

1. Oral doses (20 mg/kg) of [Me-¹⁴C] toluene-2-sulphonamide were rapidly eliminated by rats (92% of dose in 24 h). Most of the ¹⁴C (88%) was recovered in the urine within 7 days with little (5%) in the faeces. Larger oral doses (125 and 200 mg/kg) were eliminated more slowly (70 and 43% respectively in 24 h) but the overall distribution of ¹⁴C between urine and faeces was unchanged.

2. Low oral doses (0·2-0·4 mg/kg) of [Me-¹⁴C] toluene-2-sulphonamide were excreted more slowly in man than in the rat, with about 50% recovered in the urine in 24 h and 80% in 48 h. Negligible ¹⁴C (<1%) appeared in the faeces.

3. The main metabolites of toluene-2-sulphonamide were 2-sulphamoylbenzyl alcohol and its sulphate and glucuronic acid conjugates (80% of the ¹⁴C in the urine of rats and 35% in man) and saccharin (35% in man and 3% in the rat). Other metabolites found in the urine were 2-sulphamoylbenzoic acid (2% in the rat and 4% in man) and N-acetyltoluene-2-sulphonamide (6% in rat and 2% in man) together with unchanged compound (5% in rat and 3% in man).