Metabolic fate of anti-ulcer drug TEI-5103. (III). Metabolism in rats and dogs.

Tanabe, Hirofumi; Sato, Junichi; Ota, Tomohiro; Mochizuki, Takashi; Okabe, Kouichiro; Ohba, Takeo; Naruchi, Tatsuyuki

doi:10.2133/dmpk.3.25

Cited by 1 publication

(4 citation statements)

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“…Our results are consistent with the other CL metabolism studies carried out in rats, which reported CL was rapidly and extensively eliminated via urine (4,6,7). However, the amount of unchanged drug in urine found in the present study was far below the values stated previously.…”

Section: Discussionsupporting

confidence: 93%

“…However, the amount of unchanged drug in urine found in the present study was far below the values stated previously. In the Tanabe et al study (6), β-glucuronidase was used during urinary metabolites analysis, which may have led to N-OH-CL reduction, as indicated by the present results. In the earlier study of Kopitar and Zimmer (4), rats receiving a single oral dose of 2 mg/ kg of labeled CL excreted nearly 70% of the radioactivity in urine as unchanged CL.…”

Section: Discussionmentioning

confidence: 57%

“…Our results clearly indicate that the formation of (hydroxyamino)clenbuterol [4-(hydroxyamino)-3,5-dichloro-α-[( tert- butylamino)methyl]benzyl alcohol] is one of the major routes for CL metabolism in the rat. Although this pathway would appear to be possible when considering the parental compound structure ( − ), it had not been previously reported until now ( − ). Moreover, within the large range of single oral dosages tested ( ca .…”

Section: Discussionmentioning

confidence: 83%

“…Partial data concerning the biotransformation of CL in laboratory animals ( − ) have been published. The main metabolic routes for CL metabolism in the rat and dog were proposed to be sulfate conjugation on the primary amine, glucuronic acid N -conjugation on the secondary amine, hydroxylation on the tert -butyl group, and an extensive pathway leading to 4-amino-3,5-dichloromandelic acid and derived metabolites.…”

Section: Introductionmentioning

confidence: 99%

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Evidence for a New and Major Metabolic Pathway of Clenbuterol Involving in Vivo Formation of an N-Hydroxyarylamine

Zalko¹,

Debrauwer²,

Bories³

1997

Chem. Res. Toxicol.

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Clenbuterol is a beta-adrenergic agonist widely but illegally used in cattle as a growth promoter. The metabolic fate of this drug remains unknown in the main target species, i.e. the bovine, and only limited data have been published concerning its biotransformations in laboratory animals. A metabolic study has been carried out in the rat using 3H- and 14C-labeled clenbuterol. Urine appeared to be the major excretion pathway. Using a soft technique for urine preparation, extraction, and purification, as well as adequate analytical tools in order to preserve labile metabolites, N-oxidation products of the parental drug on the primary amine function were identified for the first time. Clenbuterol hydroxylamine was the major compound, but 4-nitroclenbuterol was also detected. The metabolic pathway leading to the formation of clenbuterol hydroxylamine prevails at high dosages. Clenbuterol hydroxylamine (but not 4-nitroclenbuterol) was also formed extensively when the drug was incubated with rat liver microsomal fractions in aerobic conditions. It is concluded that oxido reduction during urine preparation have previously impaired the identification of this toxicologically important clenbuterol metabolic route.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 57%