Abstract
The metabolic fate of [14C]clenbuterol was studied in male and female Wistar rats. After a single oral dose of 200 μg/kg [14C]clenbuterol, in an 8-day study period, approximately 60% of the radioactivity was eliminated in urine; 20 and 30% of the radioactivity was excreted in feces by male and female rats, respectively. HPLC coupled to on-line radioactivity detection allowed the separation and quantitation of clenbuterol metabolites, some of which were found to be poorly stable in urine. Most of the urinary and fecal metabolites of clenbuterol were isolated and identified using various MS techniques. Analytical methods were also developed to establish the metabolic profiles in feces and tissues, up to 72 hr after clenbuterol administration. Clenbuterol was mainly metabolized by N-dealkylation (secondary amine), as well as N-oxidation and sulfate conjugation (primary amine). Gender-related differences in the rates of clenbuterolN-dealkylation were observed. 4-N-Hydroxylamine was the major metabolite detected in urine, whereas more than one half of the radioactivity in feces was associated with clenbuterol sulfamate.
Footnotes
-
Send reprint requests to: Jacques Tulliez, Ph.D., Laboratoire des Xénobiotiques INRA, 180 Chemin de Tournefeuille, B.P. 3, 31931 Toulouse Cedex, France.
-
This study was supported by a grant from the Ministère de l’Enseignement Supérieur et de la Recherche, within the project “Aliment Demain” (Grant 95G0098). D.Z. gratefully acknowledges receipt of a research studentship from the Ministère de l’Enseignement Supérieur et de la Recherche.
- Abbreviations used are::
- CL
- clenbuterol
- N-OH-CL
- 4-hydroxyamino-3,5-dichloro-α-(tert-butylaminomethyl)benzyl alcohol
- NO-CL
- 4-nitroso-3,5-dichloro-α-(tert-butylaminomethyl)benzyl alcohol
- NO2-CL
- 4-nitro-3,5-dichloro-α-(tert-butylaminomethyl)benzyl alcohol
- OH-CL
- 4-amino-3,5-dichloro-α-(2-hydroxy-1,1-dimethyl)ethylaminomethylbenzyl alcohol
- SCL
- clenbuterol 4-aminosulfonic acid
- ADBA
- 4-amino-3,5-dichlorobenzoic acid
- ADHA
- 4-amino-3,5-dichlorohippuric acid
- ADMA
- 4-amino-3,5-dichloromandelic acid
- ADOA
- 2-(4-amino-3,5-dichlorophenyl)-2-oxoacetic acid
- ESI
- electrospray ionization
- FAB
- fast atom bombardment
- CID
- collision-induced dissociation
- Received August 27, 1997.
- Accepted April 29, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|