Acetamide—a metabolite of metronidazole formed by the intestinal flora

Koch, R.; Chrystal, Ewan J. T.; Beaulieu, Bernard B.; Goldman, Peter

doi:10.1016/0006-2952(79)90407-6

Cited by 104 publications

(34 citation statements)

References 10 publications

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“…Lower the effect by activating metabolism [13] Sulfasalazine Azodyes/Antibiotics Salfasalazine is a prodrug that requires activation by azoreduction, mediated by intestinal bacteria, to result in sulfapyridine and 5-aminosalisylic acid. Patients who have undergone ileostomy had lower plasma levels of sulfapyridine than controls.…”

Section: Glutathione Peroxidase 2 (Gpx2) Enzymementioning

confidence: 99%

Diet-Microbiota Interactions and their Implications for Healthy Living

2014

Health and the Gut

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The influence of resident gut microbes on xenobiotic metabolism has been investigated at different levels throughout the past five decades. However, with the advance in sequencing and pyrotagging technologies, addressing the influence of microbes on xenobiotics had to evolve from assessing direct metabolic effects on toxins and botanicals by conventional culture-based techniques to elucidating the role of community composition on drugs metabolic profiles through DNA sequence-based phylogeny and metagenomics. Following the completion of the Human Genome Project, the rapid, substantial growth of the Human Microbiome Project (HMP) opens new horizons for studying how microbiome compositional and functional variations affect drug action, fate, and toxicity (pharmacomicrobiomics), notably in the human gut. The HMP continues to characterize the microbial communities associated with the human gut, determine whether there is a common gut microbiome profile shared among healthy humans, and investigate the effect of its alterations on health. Here, we offer a glimpse into the known effects of the gut microbiota on xenobiotic metabolism, with emphasis on cases where microbiome variations lead to different therapeutic outcomes. We discuss a few examples representing how the microbiome interacts with human metabolic enzymes in the liver and intestine. In addition, we attempt to envisage a roadmap for the future implications of the HMP on therapeutics and personalized medicine.

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Section: Glutathione Peroxidase 2 (Gpx2) Enzymementioning

confidence: 99%

Diet-Microbiota Interactions and their Implications for Healthy Living

2014

Health and the Gut

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“…The column was eluted successively with 30.0 ml of water and 50.0 ml of 1 N ammonium hydroxide; 2.0-ml fractions were collected. Thin-layer chromatographic methods (9) indicated that acetamide was the sole radiolabeled compound in fractions 13 [1-'4C]acetamide was added to bacterial incubation mixtures as described above, and samples were removed periodically and filtered; 0.5-mi samples were fractionated on an AG 1-X4 column (0.9 cm by 5 cm; acetate form; Bio-Rad Laboratories). The column was eluted successively with 20.0 ml of water and 20.0 ml of 1 N hydrochloric acid; 2.0-ml fractions were collected.…”

Section: Methodsmentioning

confidence: 99%

“…Their origin is compatible with a hydrolytic cleavage between nitrogen atom 1 and carbon atom 2, as well as between nitrogen atom 3 and carbon atom 4 of the imidazole ring. We have suggested that this cleavage occurs on a partially reduced intermediate in metronidazole reduction (9). It has also been suggested that a partially reduced intermediate in metronidazole reduction is responsible for the trichomonicidal activity of this drug (7,12), and it is likely that a partially reduced intermediate is the electrophile, which could explain the weak carcinogenicity of the drug (17).…”

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confidence: 86%

Relationship between metronidazole metabolism and bactericidal activity

Chrystal¹,

Koch²,

McLafferty³

et al. 1980

Antimicrob Agents Chemother

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It has been suggested that the microbicidal effect of metronidazole is mediated by an intermediate in nitro group reduction. We have found that the addition of Escherichia coli enhances the lethal effect of metronidazole on Bacillus fragilis and suggest that this intermediate may form in one bacteria and kill another. Because acetamide forms during the reduction of metronidazole, we examined the possibility that the same partially reduced intermediate in metronidazole reduction may be both an intermediate in the formation of acetamide and the' ultimate reactive form of metronidazole which is responsible for its bactericidal action. Thus, we determined the relationship between bacterial survival and the' formation of acetamide when cultures of B. fragilis, Clostridium perfringens,'and E. coli were incubated anaerobically in the presence of metronidazole. We found that the log of the early bacterial survival was proportional to the formation of acetamide. The rate of loss of metronidazole was not dependent on the concentration of bacteria in the medium, suggesting that any proposed intermediate formed at a rate which was proportional only to the concentration of metronidazole.

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“…1, but only the latter permits an examination of possible correlations between chemical reactions and biological activities (2). Acetamide, one of the metabolites of metronidazole (6) Alternatively, the medium was prepared by combining the broth and vitamin mixture, sterilizing the mixture by filtration in a 0.45-,um Nalgene filter unit (Nalge Sybron Corp., Rochester, N.Y.), and then aseptically adding the inactivated bovine serum. The medium (13 to 14 ml) in sterile, screw-cap tubes (16 by 125 mm) was stored at 40C.…”

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confidence: 99%

“…To confirm their identity, we chromatographed the radiolabeled material in these fractions on thin-layer cellulose sheets (no. 6064, Eastman Kodak Co., Rochester, N.Y.) by using systems previously described (6), and the sheets were cut into 0.5-cm widths which were assayed for radioactivity by liquid scintillation photometry. The mobility of the radiolabel was then compared with that of authentic [1-14C]acetamide.…”

mentioning

confidence: 99%

Metronidazole Metabolism in Cultures of Entamoeba histolytica and Trichomonas vaginalis

Beaulieu¹,

McLafferty²,

Koch³

et al. 1981

Antimicrob Agents Chemother

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Acetamide forms from metronidazole in cultures of either Entamoeba histolytica or Trichomonas vaginalis as it does in cultures of bacteria which are susceptible to this drug. Under aerobic conditions, the formation of acetamide is more rapid in a strain of T. vaginalis which is more susceptible to metronidazole. Thus, it appears that the formation of acetamide may be associated with the microbiocidal action of metronidazole.

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Acetamide—a metabolite of metronidazole formed by the intestinal flora

Cited by 104 publications

References 10 publications

Diet-Microbiota Interactions and their Implications for Healthy Living

Diet-Microbiota Interactions and their Implications for Healthy Living

Relationship between metronidazole metabolism and bactericidal activity

Metronidazole Metabolism in Cultures of Entamoeba histolytica and Trichomonas vaginalis

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