Zilpaterol

Zilpaterol
Clinical data
Trade namesZilmax
Routes of
administration		Oral
ATC code
  • none
Legal status
Legal status
  • AU: S4 (Prescription only)
Pharmacokinetic data
Elimination half-life11.9–13.2 hours (first phase)
ExcretionUrine (88.2–84.3%) and feces (8.6–8.7%) (in cattle)[1]
Identifiers
IUPAC name
  • (±)-trans-4,5,6,7-Tetrahydro-7-hydroxy-6-(isopropylamino)-imidazo[4,5,1-jk]-[1]benzazepin-2(1H)-one
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC14H19N3O2
Molar mass261.325 g·mol−1
3D model (JSmol)
SMILES
  • CC(C)N[C@@H]1CCN2C3=C([C@H]1O)C=CC=C3NC2=O
InChI
  • InChI=1S/C14H19N3O2/c1-8(2)15-11-6-7-17-12-9(13(11)18)4-3-5-10(12)16-14(17)19/h3-5,8,11,13,15,18H,6-7H2,1-2H3,(H,16,19)/t11-,13-/m1/s1 ☒N
  • Key:ZSTCZWJCLIRCOJ-DGCLKSJQSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Zilpaterol (zilpaterol hydrochloride; codenamed RU 42173) is a β2 adrenergic agonist.[2][3] Under its trade name, Zilmax, it is used to increase the size of cattle and the efficiency of feeding them.[4] Zilmax is produced by Intervet, a subsidiary of Merck & Co.,[4][5] and marketed as a "beef-improvement technology".[6] Zilpaterol is typically fed in the last three to six weeks of cattle's lives, with a brief period (three days in the US) before death for withdrawal, which allows the drug to mostly leave the animal's tissues.

Concerns have been raised on the impact of zilpaterol on flavor;[7] however, studies have confirmed that overall tenderness, juiciness, flavor intensity, and beef flavor remain within the normal variation observed in the beef industry and differences are smaller than what can be detected by the consumer.[8] However, several studies have shown the use of zilpaterol leads to increased size, feed efficiency, and value.[9][10][11][12]

Merck reported Zilmax-fed cattle do not produce beef with a difference in taste or quality compared to cattle not fed the drug, but elsewhere, concerns have been raised about the beef's tenderness.[4][5] Studies have variously found a slight reduction in tenderness,[10][13] an increase in shear force,[11] and a lower percentage of intramuscular fat (marbling).[13]

Prohibitions and processor adoption

As of October 2017, Zilmax was approved in 17 countries, notably the US, Canada, South Africa, South Korea, the Ukraine and Brazil.[14]

As of 2013, Zilmax was banned in China, Taiwan, Russia, and many countries in the European Union.[15][16]

In the US

Tyson Foods was the first among the largest U.S. meatpackers to adopt Zilmax. Because of concerns about tenderness and loss of marbling, Cargill and other meatpackers resisted the practice. The next adopters were JBS and National Beef, with Cargill finally joining them in mid-2012. [17]

On August 6, 2013, Tyson Foods banned Zilmax-fed cattle from its processing plants after cattle began arriving with missing hooves in large numbers during hot weather.[18]

Origin and formulation

Zilmax is produced by Merck in France, a country in which the substance is prohibited. As of October 2017, its commercial formulation was 4.8% zilpaterol hydrochloride, 8% polyoxyl castor oil, 4.3% polyvinyl pyrrolidone and 82.9% ground corn cob.[14]

Chemistry

Zilpaterol has two chiral carbons and consequently four optical enantiomers. These enantiomers are: (6R,7R)-, (6R,7S)-, (6S,7R)- and (6S,7S)-. RU 42173 corresponds to racemic trans-zilpaterol hydrochloride, a mixture of the (6R,7R)-(−)- and (6S,7S)-(+)-enantiomers.[1]

References

  1. 1 2 Joe Boison; Fernando Ramos; Pascal Sanders; Al Chicoine; Stefan Scheid (2013). "Residue Evaluation of Certain Veterinary Drugs (78th meeting). 10. Zilpaterol hydrochloride" (PDF). Food and Agriculture Organization of the United Nations. Joint FAO/WHO Expert Committee on Food Additives. pp. 133–59. Retrieved 22 February 2016.
  2. ↑ "Zilmax (zilpaterol hydrochloride 4.8%) Type A Medicated Article". Compendium of Veterinary Products — Merck Animal Health. Intervet/Merck Animal Health. Retrieved 22 February 2016.
  3. ↑ Verhoeckx KC, Doornbos RP, Witkamp RF, van der Greef J, Rodenburg RJ (January 2006). "Beta-adrenergic receptor agonists induce the release of granulocyte chemotactic protein-2, oncostatin M, and vascular endothelial growth factor from macrophages". Int Immunopharmacol. 6 (1): 1–7. doi:10.1016/j.intimp.2005.05.013. PMID 16332507.
  4. 1 2 3 Petersen, Melody. "As Beef Cattle Become Behemoths, Who Are Animal Scientists Serving?". The Chronicle Review - The Chronicle of Higher Education. Chronicle.com. Retrieved 2012-04-16.
  5. 1 2 "Zilmax - Overview". Merck-animal-health-usa.com. Retrieved 2012-04-16.
  6. ↑ "Zilmax® Post-Approval Research Nears Completion Intervet's New Performance Technology Offers Value throughout Beef Industry". Merck Animal Health USA. July 19, 2007. Retrieved 29 July 2015. This is the first beef-improvement technology to add value all the way through the beef system.
  7. ↑ "Why Beef Is Becoming More Like Chicken". Slate.com. Feb 14, 2013.
  8. ↑ "ZILMAX (Zilpaterol Hydrochloride): Type A Medicated Article for Cattle Fed in Confinement for Slaughter" (PDF). Freedom of Information Summary, Original New Animal Drug Application, NADA 141-258. Food and Drug Administration.
  9. ↑ A. Plascencia; N. Torrentera & R.A. Zinn (1999). "Influence of the β-Agonist, Zilpaterol, on Growth Performance and Carcass Characteristics of Feedlot Steers". Proceedings, Western Section, American Society of Animal Science. 50: 331–334.
  10. 1 2 Montgomery, J. L.; Krehbiel, C. R.; Cranston, J. J.; Yates, D. A.; Hutcheson, J. P.; Nichols, W. T.; Streeter, M. N.; Bechtol, D. T.; Johnson, E.; Terhune, T.; Montgomery, T. H. (2009). "Dietary zilpaterol hydrochloride. I. Feedlot performance and carcass traits of steers and heifers". Journal of Animal Science. 87 (4): 1374–83. doi:10.2527/jas.2008-1162. PMID 19098247.
  11. 1 2 Delmore, R. J.; Hodgen, J. M.; Johnson, B. J. (2010). "Perspectives on the application of zilpaterol hydrochloride in the United States beef industry". Journal of Animal Science. 88 (8): 2825–8. doi:10.2527/jas.2009-2473. PMID 20382871.
  12. ↑ Lawrence, T. E.; Gasch, C. A.; Hutcheson, J. P.; Hodgen, J. M. (2011). "Zilpaterol improves feeding performance and fabrication yield of concentrate-finished cull cows". Journal of Animal Science. 89 (7): 2170–5. doi:10.2527/jas.2010-3422. PMID 21278106.
  13. 1 2 Holmer, S. F.; Fernández-Dueñas, D. M.; Scramlin, S. M.; Souza, C. M.; Boler, D. D.; McKeith, F. K.; Killefer, J.; Delmore, R. J.; Beckett, J. L.; Lawrence, T. E.; Vanoverbeke, D. L.; Hilton, G. G.; Dikeman, M. E.; Brooks, J. C.; Zinn, R. A.; Streeter, M. N.; Hutcheson, J. P.; Nichols, W. T.; Allen, D. M.; Yates, D. A. (2009). "The effect of zilpaterol hydrochloride on meat quality of calf-fed Holstein steers". Journal of Animal Science. 87 (11): 3730–8. doi:10.2527/jas.2009-1838. PMID 19648490.
  14. 1 2 LE BIZEC, Bruno (October 2017). "A GENERAL PERSPECTIVE ON THE USE OF WADA PROHIBITED SUBSTANCES FOR ANIMAL HUSBANDRY" (PDF). WADA.
  15. ↑ "Did Tyson Ban Doping Cows with Zilmax to Boost Foreign Sales?". NPR.org.
  16. ↑ Reuters
  17. ↑ Leonard, Christopher (2014). The meat racket : the secret takeover of America's food business. New York: Simon & Schuster. ISBN 9781451645811.
  18. ↑ "Cattle Feet Were 'Basically Coming Apart' Before Merck Halted Sales of a Muscle-Building Drug". Business Insider.
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