J. W. Bridges

The Role of the Gut Flora in the Metabolism of Prontosil and Neoprontosil in the Rat

1. The urinary excretion of total sulphanilamide (free and acetylated) in rats receiving Prontosil or Neoprontosil orally is considerably reduced when the rats are treated with antibiotics to suppress their intestinal flora. The absorption and metabolism of sulphanilamide are unaffected by such treatment with antibiotics.2. The lipid-soluble Prontosil after oral or intraperitoneal administration is partly excreted in the bile as a polar conjugate, apparently an N-glucuronide, and this drug appears to be converted into sulphanilamide partly by metabolism by the body tissues and partly by enterofloral metabolism.3. The polar, water-soluble Neoprontosil is poorly absorbed from the intestine and when given orally is largely reduced to sulphanilamide by the gut flora before absorption. When given intraperitoneally, a large proportion (up to 70%) of the drug is excreted in the bile unchanged, and it would appear that only a small proportion of the drug (ca. 20%) is converted to sulphanilamide in the tissues, th...

The Conjugation of Indolylacetic Acid in Man, Monkeys and other Species

Indol-3-yl[2-14C]acetic acid has been administered to 18 species of animals including man, and the urinary metabolites examined by radiochromatogram scanning. Man received 500 mg orally and the other animals 100 mg/kg by intraperitoneal injection.In most species, 50–90% of the administered 14C was excreted in the urine in 48 h. 14–76% of the indolylacetic acid was excreted unchanged in 48 h.In man, the 14C excreted in 48 h consisted of about 50% unchanged indolylacetic acid, 30% indolylacetylglucuronide and 10–20% indolylacetyl-glutamine. No glycine conjugate was detected.The glutamine conjugate was excreted only by the Old World (3 species) and New World (3 species) monkeys and man.The glycine conjugate was excreted by all species (13) except man, Old World monkeys and the pigeon. The three species of New World monkeys formed both the glutamine and glycine conjugates.Taurine conjugation of indolylacetic acid was studied in the green monkey, the squirrel monkey, the capuchin monkey, the ferret and pigeon....

Intestinal Azo-reduction and Glucuronide Conjugation of Prontosil

Abstract1. 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...

The Enzymic Deacetylation of 4-Acetamidobenzoic Acid by Rat Tissues and the Effect of Manganese Ions

1. The enzymic deacetylation of 4-acetamidobenzoate by the liver and kidney of the rat, rabbit, mouse and guinea-pig has been examined. The most active tissue was rat kidney which was examined in detail.2. In the rat kidney the enzyme activity was found in the cell sap. This activity was considerably increased by Mn2+ ions but completely inhibited by Hg2+ ions.3. The Mn2+ ion dependent activity, but not the Mn2+ ion independent activity, was inhibited by p-chloromercuribenzoate, thioglycollate, CoA, acetyl-CoA, storage at 5°, Sephadex filtration and dimethylsulphoxide. It is suggested that Mn2+ ions activate the enzyme allosterically.4. 4-Acetamidobenzoate deacetylase activity was not found in rat brain, blood or skeletal muscle and only low activity was found in liver, heart muscle, spleen and lung.5. The rat kidney cell sap enzyme had only slight activity towards acetanilide and none towards N4-acetylsulphanilamide. Acetanilide was deacetylated mainly by the microsomal fraction of rat kidney homogenates.