The Excretion of [³⁵S]Dapsone and its Metabolites in the Urine, Faeces and Bile of the Rat

Abstract

1. When [³⁵S]dapsone was given orally to rats, 60–70% of the ³⁵S was excreted in 6 days, 45% in the urine and 22% in the faeces. The bulk of the ³⁵S was excreted in the first 24 h. Values were similar but slightly higher when the compound was given intraperitoneally.

2. When [³⁵S]dapsone was given intraperitoneally to bile duct-cannulated rats, 75–80% of the ³⁵S was excreted in 3 days, 32% in the bile and 27% in the urine.

3. The main metabolite in the urine was dapsone N-sulphamate, with smaller amounts of dapsone, acetyldapsone, N-acetyldapsone N'-sulphamate and dapsone N-glucuronide, whereas the main metabolite in the bile was dapsone N-glucuronide with only small amounts of N-sulphamate.

4. The amount of dapsone N-glucuronide detected in the urine increased when the rats were given NaHCO₃ to produce an alkaline urine.

5. The difference in the nature of the major metabolite found in the urine and that found in the bile has been explained in terms of the instability of N-glucuronides at acid pH and the molecular weight values required for significant biliary excretion in the rat, the N-glucuronide having a higher molecular weight than the N-sulphamate.

6. The potassium salts of dapsone N-sulphamate, dapsone N, N'-disulphamate, and N-acetyldapsone N'-sulphamate have been synthesized.