Intestinal Azo-reduction and Glucuronide Conjugation of Prontosil

Abstract

1. The lipid-soluble azo-dye Prontosil was excreted in rat bile as an N-glucuronide, and in the urine, after azo-reduction, as free and N⁴-acetylated sulphanilamide.

2. When everted sections of rat intestine were incubated with ³⁵S-Prontosil, the dye was metabolized mostly to the glucuronide and partly to sulphanilamide by the intestinal wall.

3. Both intravenously and intraduodenally administered ³⁵S-Prontosil to biliary cannulated rats was recovered mainly in the bile as the N-glucuronide, whereas intracaecally administered ³⁵S-Prontosil was recovered chiefly in the urine as the products of azo-reduction. Considerably more N-glucuronide was biliary excreted after intraduodenal than intravenous dosage. The results imply that the rat intestinal wall is a major site of glucuronide conjugation of orally administered Prontosil. It is also apparent that the caecal bacteria, and not the liver, is the prime site of azo-reduction of Prontosil, in vivo. Azo-reduction is probably also mediated to some extent by the intestinal wall.

4. Urinary metabolites of ³⁵S-Prontosil from mouse, hamster and guinea-pig were qualitatively the same as the rat, although there were some quantitative differences.