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P Millburn

Publications and source records attributed to P Millburn.

58 records · Page 4Linked to original sources
PubMedDate not supplied

Species differences in the metabolism of 3-phenoxybenzoic acid.

The metabolism of 3-phenoxybenzoic acid (3PBA) (10 mg/kg, ip) has been studied in ten mammalian and one avian species in comparison with that of benzoic acid. 3PBA exhibits wide species diversity in its metabolism, unlike benzoic acid, of which benzoylglycine (hippuric acid) is the major urinary metabolite in all species studied. With 3PBA, glycine conjugation is the major route of metabolism in three species (sheep, cat, and gerbil), whereas in the mouse the taurine conjugate is the principal metabolite. The ferret eliminates similar amounts of each of these metabolites, whereas the glycylvaline dipeptide conjugate is the major metabolite isolated from the excreta of the mallard duck. Conversely, glucuronic acid conjugates of 3PBA and its 4'-hydroxy derivative (4'HO3PBA) are the major urinary metabolites in the marmoset, rabbit, guinea pig, and hamster; the rat appears unique in eliminating the O-sulfate conjugate of 4'HO3PBA as the principal urinary metabolite. In most cases, where amino acid conjugates are the major excretory products, the proportions of hydroxylated metabolites present are minimal. The pattern of metabolism of 3PBA does not significantly vary with dose (0.1-100 mg/kg) or route (ip and po) in the sheep, gerbil, or mouse. When administered 4'HO3PBA, the gerbil and mouse eliminate principally glucuronide and sulfate conjugates rather than amino acid conjugates, which are only minor components (less than 10% of the dose) in each case. This implies that hydroxylation is a primary metabolic event in determining the eventual fate of 3PBA in many species.

Administration, Oral↗
PubMedDate not supplied

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

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.

Animals↗
PubMedDate not supplied

Formation of an N-acetylornithine conjugate of 3-phenoxybenzoic acid in the chicken.

The principal metabolite detected in the excreta of chickens treated orally with 3-phenoxybenzoic acid is alpha-N-acetyl-delta-N-(3-phenoxybenzoyl)-L-ornithine. This conjugate has been isolated and purified by preparative HPLC and its structure authenticated by mass and NMR spectrometry. Although diacyl ornithine conjugates of aromatic carboxylic acids are formed in some bird species, monosubstituted derivatives are rare. Moreover, this is the first example of the occurrence of an N-acetylornithine conjugate in the biotransformation of a xenobiotic in animals. The conjugation of such nonnutritive acids in avian species is discussed.

Amino Acids↗