Metabolism of 3-phenoxybenzoic acid and the enterohepatorenal disposition of its metabolites in the rat

Journal Article · · Drug Metab. Dispos.; (United States)

OSTI ID:5439845

Huckle, K R; Chipman, J K; Hutson, D H; Millburn, P

The absorption, metabolism and disposition of 3-phenoxybenzoic acid (3PBA) and its 4'-hydroxylated derivative (4'HO3PBA) have been investigated in intact and bile duct-cannulated rats. Both acids are rapidly and extensively eliminated in the urine as the O-sulfate ester of 4'HO3PBA (4'HOSO2O3PBA). Biliary excretion was 45% of the dose when 3PBA was administered at 100 mg/kg, compared with 16% at 10 mg/kg. The major biliary metabolites, identified by mass spectrometry, were 3PBA glucuronide and the ether and ester glucuronic acid conjugates of 4'HO3PBA. These biliary metabolites were of minor importance in the urine. At a dose of 100 mg/kg, an apparent excretion balance figure approximately 120%, as determined from the extent of elimination of radioactivity in the urine (72%) of intact animals and bile of cannulated rats (45%) (only 7% appeared in the feces), suggests that the biliary glucuronides decompose and/or are enzymically cleaved in the gastrointestinal tract to the respective benzoic acids. The latter are subsequently reabsorbed and undergo further metabolism, principally to the sulfate ester which is excreted in the urine. This enterohepatorenal disposition of 3PBA has been confirmed by suppression of the gut microflora with antibiotics in vivo, which dramatically reduces the extent of deconjugation of biliary glucuronides and hence reabsorption of the free benzoic acids. The deconjugation by gut bacteria has also been demonstrated in vitro.

• OSTI ID: 5439845
• Journal Information: Drug Metab. Dispos.; (United States), Journal Name: Drug Metab. Dispos.; (United States) Vol. 9:4; ISSN DMDSA
• Country of Publication: United States
• Language: English

Related Subjects

550601 -- Medicine-- Unsealed Radionuclides in Diagnostics
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BENZOIC ACID
BILIARY TRACT
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
DIGESTIVE SYSTEM
GASTROINTESTINAL TRACT
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
METABOLISM
METABOLITES
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
RATS
REACTION KINETICS
RODENTS
TRACER TECHNIQUES
URINE
VERTEBRATES
WASTES