Hippuric acid excretion

Toluene exposure does not result in the hematopoietic effects caused by benzene. The myelotoxic effects previously attributed to toluene are judged by more recent investigations to be the result of concurrent exposure to benzene present as a contaminant in toluene solutions. Most of the toluene absorbed from inhalation is metabolized to benzoic acid, conjugated with glycine in the liver to form hippuric acid, and excreted in the urine. The average amount of hippuric acid excreted in the urine by persons not exposed to toluene is approximately 0.7-1.0 g/1 of urine. ... 

Disposition in the Body. Rapidly hydrolysed to benzoic acid and benzyl alcohol benzyl alcohol then undergoes further oxidation to benzoic acid followed by conjugation with glycine to form hippuric acid. Excreted in the urine mainly as hippuric acid. 

These substances are all excreted in normal human urine (535) and are thought probably to arise from bacterial action, but not all the transformations postulated by Baumann are probable. For example, as we shall see below, phenol is formed directly from tjirosine. Though benzoic and p-hydroxybenzoic acids can be formed from phenylalanine and tyrosine, for example, by Pseudomonas species (346, 833), a plant rather than bacterial origin has been suggested for the benzoic acid moiety of the hippuric acid excreted by man (59). 

The interaction of /2-hexane with toluene and trichloroethylene has also been examined in volunteers (Baelum et al. 1998). Exposure in these experiments was via a gastric feeding tube at controlled rates equivalent to what the authors stated would be delivered to the liver by inhalation exposure at Danish occupational exposure limits (50 ppm /7-hexane. 50 ppm toluene, and 30 ppm trichloroethylene). Coexposure to toluene and trichloroethylene slightly increased the area under the curve (AUC) representing concentration versus time for end exhaled /2-hexane air concentration, but urinary excretion of 2,5-hexanedione was unchanged. The only statistically significant interaction observed with /2-hexane was an 18% decrease in the urinary excretion of hippuric acid, a toluene metabolite. 

Ginkgo extract has no effect on the hepatic microsomal drug oxidation system, as measured by antipyrine elimination, even at doses of 400 mg per day (Duche et al. 1989). Ginkgo metabolites, the substituted benzoic acids (4-hydroxybenzoic acid conjugate, 4-hydroxyhippuric acid, 3-methoxy-4-hydroxyhippuric acid, 3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, hippuric acid and 3-methoxy-4-hydroxybenzoic acid [vanillic acid]), are excreted in urine (Pietta et al. 1997). 

Benzoic acid is metabolized in the liver by conjugation with glycine, and is rapidly excreted in the urine as hippuric acid in most of animal species. It can also be excreted as benzoilglucoronic acid when ingested in a large dose. Benzoic acid can be found in urine as a metabolite of benzaldehyde and numerous other compounds [4, 48]. 

After oral administration of 7- C-2,6- H-benzoic acid in healthy human subject (4.2 mg/kg), the drug was found to be quantitatively biotransformed to hippuric acid and excreted in urine within 4 hours [43]. 

Clifford, M.N., Copeland, E.L., Bloxsidge, J.P., and Mitchell, L.A., Hippuric acid is a major excretion product associated with black tea consumption, Xenobiotica, 30, 317, 2000. 

Mulder, T.P., Rietveld, A.G., and van Amelsvoort, J.M., Consumption of both black tea and green tea results in an increase in the excretion of hippuric acid into urine. Am. J. Clin. Nutr., 81, 256S, 2005. 

The metabolism of cinnamyl anthranilate in rats and mice has been studied (Keyhanfar Caldwell, 1996). Male Fischer 344 rats and male CD-I mice were given 250 mg/kg bw [3- C] cinnamyl anthranilate by intraperitoneal injection. The majority of the administered C was excreted in the 0-24-h urine (70% of the dose in rats and 78% in mice). A further 10% (rat) and 6% (mouse) was recovered in the 24-72-h urine with 10% (rat) and 7% (mouse) in the 0-72-h faeces. In the rat, the major urinary metabolite was hippuric acid (95% of urinary C), together with much smaller amounts of benzoic acid. However, in mice, the urine contained relatively less hippuric acid ( 80%) and more benzoic acid (16% of urinary i C), together with 2.2% of the dose as unchanged ciimamyl anthranilate. 

The influence of dose size was also examined in male and female B6C3Fi mice given 0, 10, 100, 1000, 5000, 15 000 or 30 000 ppm (mg/kg diet) ciimamyl anthranilate in the diet for four days (Caldwell et al., 1985). The urinary excretion of cinnamyl anthranilate, hippuric acid and anthranilic acid within 24-h after removal of the test diet rose with increasing cinnamyl anthranilate dose. Cinnamyl anthranilate was detected in increasing quantities in the urine of male mice at 1000 ppm and above. In females, it was only seen at 5000 ppm and above and the levels were two- to nine-fold lower. 

Methenamine mandelate is the salt of mandelic acid and methenamine and possesses properties of both of these urinary antiseptics. Methenamine hippurate is the salt of hippuric acid and methenamine. Below pH 5.5, methenamine releases formaldehyde, which is antibacterial. Mandelic acid or hippuric acid taken orally is excreted unchanged in the urine, in which these drugs are bactericidal for some gram-negative bacteria when pH is less than 5.5. 

Lof, A., Wigaeus Hjelm, E., Colmsjo, A., Lundmark, B.-O., Norstrom, A. Sato, A. (1993) Toxicokinetics of toluene and urinary excretion of hippuric acid after human exposure to -Hg-toluene. Br. J. ind. Med., 50, 55-59... 

Amphetamine is metabolized by deamination, oxidation, and hydroxylation. Figure 4.1 illustrates the metabolic scheme for amphetamine. Deamination produces an inactive metabolite, phe-nylacetone, which is further oxidized to benzoic acid and then excreted in urine as hippuric acid and glucuronide conjugates. In addition, amphetamine is also converted to norephedrine by oxidation and then this metabolite and the parent compound are / -hydroxylated. Several metabolites, including norephedrine, its hydroxy metabolite, and hydroxy amphetamine, are pharmacologically active. The excretion of amphetamine depends on urinary pH. In healthy men who were administered 5 mg of isotopically labeled d,l-amphetamine, approximately 90% of the dose was excreted... 

Cranberry enhances the excretion of hippuric acid, a bacteria-fighting chemical. Recent studies support the speculation that eating cranberries or drinking their juice can prevent or fight urinary tract infections. Hippuric acid prevents Escherichia coli (E. coli) from adhering to the urinary tract. Cranberries also contain arbutin, which fights yeast infections. The berries are also used as a urinary deodorant. ... 

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