Categorie:SympathicomimeticumJonathan Breyne Menen4 januari is een Belgische wielrenner. In won Breyne het Belgisch kampioenschap tijdrijden voor beloften. Zijn debuut bij cpenbuterol professionals maakte hij in voor Landbouwkrediet. Op 30 december won hij clenbuterol wiki nl Belgisch kampioenschap achter de derny. In november testte hij positief op clenbuterol in de Ronde van het Taihu-meereen rittenkoers in China waar hij achtste clenbuterol wiki nl.
Clenbuterol First draft prepared by Dr. C 12 H 19 OCl 3 as hydrochloride Molecular weight: Colourless microcrystalline powder Merck Index White or slightly yellowish substance sponsor Melting point: The recommended treatment schedule is 0. The maximum duration of treatment in non-lactating cattle is 10 days. It may be administered by the oral or intravenous routes of administration. Cattle may also be injected by the intramuscular route.
Clenbuterol is also used as a tocolytic in cattle. The recommended treatment schedule is a single parenteral injection equivalent to 0. Plasma Clenbuterol was well absorbed after oral administration to laboratory animals, humans and the target species. Peak plasma concentrations range 0. The plasma half-life in cattle varied from 16 to hours depending on the subpopulation tested. Excretion into Faeces and Urine Laboratory Animals and Horses After oral administration of 14 C-Clenbuterol the radioactivity was quickly distributed throughout the tissues of rats and mice and shown to cross the placental barrier of the mouse Kopitar , the dog 0.
The excretion of 14 C-Clenbuterol after oral administration is summarised in Table 1. The results indicate that the major fraction of the drug is excreted into the urine.
Similar patterns of excretion were observed if the drug was administered parenterally or by inhalation Huntingdon Res.
Cattle Eight studies Nos. IS days B 1 9 preruminant calves 0. IS 1, 7, 10 Hawkins et al, b oral x 7 3 2 9 ruminant calves 0. IS 2h, 2, 5 Hawkins et al, a oral x 5 5 1 cow 1. Fc Schmid, 9 3 cows 0. There was greater amount of metabolism in the rat compared to the other species tested. The contribution of Clenbuterol to the total residues found in urine after the administration of 14 C-Clenbuterol to several species is shown in Table 3.
Excretion of residues into the urine Species. The results are shown diagrammatically in Figure 1. The authors concluded that the biotransformation of Clenbuterol is slow relative to other b -agonists , since there are no direct points of access for the enzymes, monoamine oxidase and catechol-O-methyl transferase, or for efficient sulphate conjugation.
The main metabolites were formed by oxidation along the long side chain in the 1 position of the ring, while the 2-amino-3,5-dichloro moiety remains intact. Metabolic Profile of Clenbuterol in Dog Urine Metabolism in Cattle The metabolite profile seen in cattle is qualitatively similar to that seen in laboratory animals and in humans. Other metabolites quantified in urine included N-AB ca.
Metabolism of radiolabeled Clenbuterol in bovine liver followed a similar pattern with the majority of the extractable residues being Clenbuterol. The resulting profiles from several studies are shown in Table 4. UD is the unchanged drug, clenbuterol. The data in Table 4 are used to calculate the content of Clenbuterol as a percentage of the total residues and the results are given in the last column of Table 5.
There are differences in the values for the two methods. Selected tissues from the radiodepletion studies were analysed by a GC-MS method for the content of Clenbuterol Schmid, b.
The results are shown in Table 5. The metabolite pattern in urine obtained during a repeat-dose residue study Hawkins et al. At later sacrifice time points there was a quantitative change in the metabolite pattern observable, though not a qualitative one. The metabolism of clenbuterol in horse kidney is similar to the one described for liver.
The studies used are those numbered in Table 2; 1,2 and 3 for calves and 4, 7 and 9 for cows. Depletion of total residues is rapid in all edible tissues of calves and cows see Table 6 for references and results.
In calves, the results from GLP-certified total balance studies No. The calves in study 3 received the dose of clenbuterol hydrochloride for the maximum time as intended for the respiratory preparation, In cows there are three studies. Study 9 is an in-house orientation study in three cows; study 4, GLP-certified, concerns total balance following repeated doses of clenbuterol hydrochloride.
These demonstrate rapid depletion of radioactivity from edible tissue. Study 7, GLP-certified, confirms this using a total of 9 lactating dairy cows which received the recommended single injection of clenbuterol hydrochloride, as intended for the tocolytic preparation. Total Residues at the Injection Site In several of the studies in which Clenbuterol is administered intramusculary there were both single and multiple injections.
In one study in calves, 21 injections of 0. Samples were collected from the multiple sites and analysed for total residues radioactivity. Because the injections were given at different times data for a wide range of times after dosing is possible even in the same calf.
The results are plotted in figure 2 for time after injection versus the residue. There is a wide variation in the results and there is no correlation between time after dosing and the concentration of residues at the injection sites, in fact the residues found at hours were as high as those seen at 6 hours after injection.
The same sampling schedule was not followed in a later study Hawkins et al. Radioactive residues at intramuscular injection sites of calves Residues in Milk In a GLP study using 9 Friesian cows, mean body weight kg, the cattle were divided into groups of 3 and given a single dose of 0.
Three cows were slaughtered for tissue residue analysis before the milk was collected and the residues in the milk for the remaining 6 cows were measured. The results are shown in Table 8. The results for the total residues and clenbuterol are summarised in Table 8. For the first days after the end of treatment, most of the residues in milk consisted of unmetabolised clenbuterol.
The very low concentrations 0. The LOQ claimed for the method is 0. They were then given twice daily oral doses on days and a single oral dose on day 6. The total residues in the milk reached peak values of 3. The residues in milk of this cow collected at 12 hour intervals twice a day milkings after the last dose were: These high and persistent residues in milk clearly support the contraindication for this particular therapeutic use in lactating cows.
Horse Residues in the edible tissues were determined in three horses receiving oral doses of a formulation combining clenbuterol hydrochloride with two antibiotics. The animals were treated twice daily for ten days and then a final oral dose on day 11 see Study 10 Table 2. A similar study, however, applying only clenbuterol hydrochloride, was carried out using 12 horses and administering 21 oral doses see Study 11 Table 2.
The results are shown in Table 9. The total residues were highest in liver and kidney, very low in muscle and not detectable in fat.
Other Residue Depletion Studies with unlabeled drug Stability of Residues The effect of cooking on the heat stability of clenbuterol was investigated Rose et al. The effect of a range of cooking processes boiling, roasting, frying, microwaving on clenbuterol residues in fortified and incurred tissue was studied.
No net change in the amount of clenbuterol was observed in any of the cooking processes investigated except for deep frying using extreme conditions. There was little observed migration from the tissue into the surrounding liquid or meat juices.
Clenbuterol residues were found not to be evenly distributed in the incurred raw tissue used for the investigation.
The findings of this investigation show that data obtained from measurements on raw tissue are applicable for use in consumer exposure estimates and dietary intake calculations. Depletion Studies There were no studies submitted by the sponsor but numerous studies are reported in the open literature. These include studies using the recommended therapeutic dosage and numerous studies in which clenbuterol was administered at a dose ca.
The general conclusions were that residues of unchanged clenbuterol accumulate in the eyes, lungs, hair and feathers. The highest residues in the "basket" tissues were found in the liver and kidney.
The residues of clenbuterol in tissues and body fluids were measured in cattle treated with the therapeutic dose of the drug Elliott et al, During treatment many tissues and body fluids contained residues of clenbuterol.
After a 14 day withdrawal period residues of clenbuterol were detectable only in the eyes mean The authors conclude that it is not possible to differentiate between the legal and illegal use of the drug solely on residue analysis. This is in contrast to the opinion of the sponsor who believes that differentiation between legal and illegal use would be possible based on liver analysis, if the analytically determined concentrations of clenbuterol were related to the withdrawal time claimed to have been observed by the farmer.
Analyses of clenbuterol concentrations in different tissues was done by enzyme immunoassay EIA. Tissue samples were taken from three calves on the last day of administration and from two more after 3. Highest levels were always found in the eye: The amount of bound residues is small and insufficient to be taken into account in the calculation of MRLs.
Confirmation of positives is performed using specific GCMS methods with sensitivities for edible tissues from 0. Accuracy and precision were determined for fortified bovine tissue samples: This method was also validated for bovine and equine liver by Hawkins et al a, with acceptable accuracy and precision at the LOQ of 0.
The method proposed by the sponsor is based on GC-MS. Samples of muscle and liver were prepared by maceration and digestion with enzymes subtilisin followed by extraction with reversed phase material C Sep-Pack , cleanup by solvent distribution and derivatisation silylation.
A very similar method is described for milk Schmid, a. Specificity was demonstrated against matrix "blanks". It was shown that trimethoprim and sulfadiazine, which may be co-administered with clenbuterol, did not interfere with the assay. Clenbuterol metabolites have different lipophilicity, and molecular weights and so would not be expected to interfere. The LOQ was stated to be 0.