Effects of drugs which influence Renal transport systems on the urinary excretion of the β₂‐adrenoceptor agonist clenbuterol and the anabolic steroids ethinylestradiol and methyltestosterone

Abstract

The aim of this study was to determine whether the illegal application of clenbuterol, ethinylestradiol and methyltestosterone in cattle as growth promoter s can be concealed by co‐treatment with drugs that affect urinary excretion. Six male veal calves werefed with 0.8 μg clenbuterol kg⁻¹ of body weight (BW), 3.5 μg ethinylestradiol kg⁻¹ BW and 35 μg methyltestosterone kg⁻¹BW together twice daily for 28 days. At the eighth day of clenbuterol, ethinylestradiol and methyltestosterone treatment each calf was additionally fed either with probenecid, para‐aminohippuric acid, trimethoprim, famotidine or cimetidine at three different doses which were increased in weekly intervais. During the treatment 24 h‐urine and blood samples (once daily) were obtained and analysed for clenbuterol, ethinylestradiol and methyltestosterone by specific enzyme immuno‐assay. By high performance liquid chromatography/ enzyme immunoassay it was determined whether these drugs or their metabolites interfered with the immuno‐logical detection of the growth promoters. Clenbuterol, ethinylestradiol and methyltestosterone could be de‐tected in plasma and urine throughout the whole experiment. Co‐treatment with probenecid led to a five‐fold reduction in urinary excretion of ethinylestradiol and co‐treatment with trimethoprim led to a three fold reduction in urinary excretion of clenbuterol. None of the drugs reduced urinary excretion of the growth Promoters to concentrations below the limit of detection. The detection of these three growth promoters in urine samples from calves which were co‐treated with the drugs tested in this study can thus not be prevented.

Keywords:

• ethinylestradiol
• methyltestosterone
• probenecid
• para‐aminohippuric acid
• trimethoprim
• famotidine
• cimetidine
• urinary excretion
• enzyme immunoassay
• HPLC

Notes

To whom correspondence should be addressed at: Institut für Physiologie, Forschungszentrum für Milch und Lebensmittel Weihenstephan, Vöttinger Straße 45, D‐85350 Freising, Germany.