A major rat faecal metabolite of ipronidazole

Weiss, George B.; Rose, Nathan R.; Duke, Paul D.; Williams, Thomas H.

doi:10.3109/00498258109045293

Cited by 8 publications

(3 citation statements)

References 4 publications

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Section: Discussionmentioning

confidence: 99%

“…From these observations it seems likely that any Nmethylimidazole would liberate methylamine under the assay conditions. Thus, all conceivable metabolite products which have not been degraded to a single carbon fragment would yield radioactive methylamine [including the unique fecal metabolite, 2,3-dihydro-2-(2-hydroxypropyl)-3-methyl-4-nitrc-1H-imidazol-5-01, recently isolated from ipronidazole by Weiss et al (1981)]. From the methylamine liberation analyses in Table V it can be seen that for on-drug samples, about 90% of the radioactivity present in muscle and 70% of that in liver liberates radioactive methylamine.…”

Section: Disposition Of Ronidazole In Swinementioning

confidence: 99%

See 1 more Smart Citation

Disposition of ronidazole by swine. I. Radiocarbon content of tissues

Wolf¹,

Baylis²,

Smith³

et al. 1983

J. Agric. Food Chem.

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The antiparasitic and antibacterial compound, ronidazole (( l-methyl-5-nitroimidazol-2-yl)methyl carbamate), was rapidly absorbed and excreted by the pig after oral administration of 14CH3-labeled drug. Of the total excreted, less than half of the radioactivity was present in the urine. Radioactive residues were ubiquitously distributed in all tissues analyzed. Radioactive residues were present in edible tissues 42 days after dosing and were associated with tissue proteins. The relative depletion rates of different tissues is suggestive of the incorporation of endogeneous metabolites. Liberation of labeled methylamine by acid hydrolysis indicated that as much as 20-30% of the persistent residues retain some chemical relationship to the drug. As the fraction of the persistent residues which liberate methylamine declined with time, at least two general types of residues are present. Further studies using nitric acid oxidation of the residues showed that the fraction containing an intact 1-methyl-5-nitroimidazole nucleus was about 1% of the total residue.Ronidazole [ (l-methyl-5-nitroimidazol-2-yl)methyl carbamate] is a nitroimidazole useful in animal husbandry. Metabolic studies in the turkey have been reported (Rosenblum et al., 1972). These studies showed extensive metabolic degradation with resultant persistent radioactivity in various tissues, especially muscle. Since evolution of 14C02 was reported as 2.5% when the label was at the 2-ring atom and only 0.8% when the CH3 was labeled, 14CH3-labeled ronidazole was used in the current studies except that one animal was dosed with 2-ring-labeled ronidazole. The current studies were designed to determine the distribution of drug and metabolites in edible tissues of the pig, the depletion of radioactive residues with time, and the macromolecular nature of the tissue residue due to ronidazole. Chemical degradation studies designed to determine if the radioactive residues were due exclusively to metabolic degradation to single carbon fragments were carried out. MATERIALS AND METHODS Chemicals.Radiolabeled ronidazole was synthesized in the Merck Sharp & Dohme Research Laboratories. All lots were analyzed for radiochemical purity by paper or thin-layer chromatography and had a radiochemical purity of greater than 98% when used. No single impurity was present in a quantity greater than 0.5%. The specific activity was adjusted for each experiment to a suitable level by dissolving unlabeled and labeled material and either dosing the resultant solution or crystallizing the product before use.14CH3-Labeled ronidazole was synthesized from 14CH30H by treatment with methanesulfonic acid anhydride. The methyl methanesulfonate reacted with 4-nitroimidazole to yield predominantly [methyP4C]-lmethyl-5-nitroimidazole. Reaction with formaldehyde followed by transesterification with methylcarbamate yielded [methyl-14C] ronidazole.Ring 2-labeled ronidazole was synthesized from [2-l4CIimidazole obtained by reaction of ethylenediamine and [14C]formic acid at 500 "C via the usual steps of ...

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Section: Discussionmentioning

confidence: 99%

Section: Disposition Of Ronidazole In Swinementioning

confidence: 99%

Disposition of ronidazole by swine. I. Radiocarbon content of tissues

Wolf¹,

Baylis²,

Smith³

et al. 1983

J. Agric. Food Chem.

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“…Actually, most of the drug-related metabolites of many 5-nitroimidazoles in mammals have an intact nitro group (Assandri et al, 1978;Voogd, 1981;Weiss et al, 1981) and antimicrobial activity. This suggests that many 5-nitroimidazoles are not reduced in animal tissues if the usual therapeutic doses are administered.…”

Section: Pharmacological Mode Of Actionmentioning

confidence: 99%

Pharmaco‐Toxicological Mode of Action of Antimicrobial5‐Nitroimidazole Derivatives

Schmid¹,

Schmid²

1999

Journal of Veterinary Medicine Series A

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5-Nitroimidazole derivatives are used as therapeutic agents against anaerobic microorganisms which are pathogenic to man and animals.The antimicrobial mode of action of these compounds is due to the metabolic reduction of the nitro group by microbial metabolism.By analogy, a reduction of the 5-nitro group in the aerobic animal metabolism is commonly assumed. This assumption is doubtful in its general form, and a more differentiated view is presented.

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The Chemistry of Nitroimidazole Hypoxic Cell Radiosensitizers

Smithen

Hardy

1982

Advanced Topics on Radiosensitizers of Hypoxic Cells

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A major rat faecal metabolite of ipronidazole

Cited by 8 publications

References 4 publications

Disposition of ronidazole by swine. I. Radiocarbon content of tissues

Disposition of ronidazole by swine. I. Radiocarbon content of tissues

Pharmaco‐Toxicological Mode of Action of Antimicrobial5‐Nitroimidazole Derivatives

The Chemistry of Nitroimidazole Hypoxic Cell Radiosensitizers

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