Clenbuterol plasma concentrations after therapeutic administration in fit Standardbred horses: threshold recommendations
In: Comparative Exercise PhysiologySearch for other papers by K.H. McKeever in
Current site
Google Scholar
Search for other papers by H.C. Manso Filho in
Current site
Google Scholar
Search for other papers by E.M. Rankins in
Current site
Google Scholar
Search for other papers by C.S. Duchamp in
Current site
Google Scholar
Search for other papers by Y. Salah in
Current site
Google Scholar
Search for other papers by C.K. Fenger in
Current site
Google Scholar
Search for other papers by W.C. Duer in
Current site
Google Scholar
Search for other papers by K. Malinowski in
Current site
Google Scholar
Search for other papers by G.A. Maylin in
Current site
Google Scholar
Clenbuterol, (RS)-1-(4-amino-3,5-dichlorophenyl)-2-(tert-butylamino)ethan-1-ol, as Ventipulmin is an FDA approved β2 agonist medication for the management of airway obstruction in horses. Administration above the FDA approved doses for clenbuterol produces repartitioning effects, which have led to restrictions on its use in human athletics and Quarter Horse and Thoroughbred racing. Clenbuterol, however has long been used therapeutically at FDA approved doses in Harness racing. The goal of this study was to identify a withdrawal time guideline for its use at FDA approvsed dose levels in Harness racing, where horses may start at seven-day intervals. Eight healthy, moderately fit Standardbred horses (4 mares, 4 geldings, weight 491±40 kg, age 13±2 years) were administered 0.8 μg/kg of clenbuterol as Ventipulmin syrup twice daily (BID) for three days. Blood samples were collected prior to dosing and at 1, 24, 48 and 96 h post administration. Clenbuterol was quantified in all samples using the New York Drug Testing and Research Laboratory ISO-17025 Racing and Medication Testing Consortium (RMTC) accredited quantitative procedure. The lower limit of quantitation of the method was 1.0 pg/ml, and three data points at 96 h post administration were censored. One horse developed diarrhoea and data from this horse was excluded from the overall analysis. Plasma regulatory thresholds were calculated using the 95/95 tolerance method and Gauss Camp Meidell at P=0.05 and P=0.001. Horses were also evaluated for effects of clenbuterol on body composition using body mass and ultrasound measurements of rump fat thickness. There were no effects (P>0.05) of clenbuterol on any of the measures including fat mass and fat free mass and thus no repartitioning effect was observed. The pharmacokinetic data and the 96 h data set support the therapeutic use of clenbuterol in Harness horses at the FDA approved 0.8 μg/kg BID dose for three days and suggest a 41 pg/ml regulatory threshold for a 96 h withdrawal time with a P=0.001 probability of randomly exceeding this regulatory threshold.
-
Anonymous, 2015. AQHA makes clenbuterol a banned substance. Quarter Horse News, 2 September 2015. Available at: https://tinyurl.com/y42kdnes
-
Association of Racing Commissioners International (ARCI), 2020. Drug testing standards and practices program. Uniform classification guidelines for foreign substances and recommended penalties model rule. January 2020 (V.14.1). Available at: https://tinyurl.com/y4w6cyxh
-
Collett, L., Kamerling, S., Woods, W.E., Weckman, T., Nugent, T., DeQuick, D. and Tobin, T., 1983. Clearance times and behavioral effects of clenbuterol in the horse. In: Proceedings of the 5th International Conference of Cont. Use Drugs Racehorses. Toronto, Canada, pp. 265-271.
Clearance times and behavioral effects of clenbuterol in the horse 265 271
-
Couëtil, L.L., Cardwell, J.M., Gerber, V., Lavoie, J.-P., Léguillette, R. and Richard, E.A., 2016, Inflammatory airway disease of horses – revised consensus statement. Journal of Veterinary Internal Medicine 30: 503-515. https://doi.org/10.1111/jvim.13824
-
Harkins, J.D., Robinson, N.E., Woods, W.E., Lehner, A.F., Smith, M.D., Gates, R.S., Fisher, M. and Tobin, T., 2000. Intratracheal clenbuterol in the horse: its pharmacological efficacy and analytical detection. Journal of Veterinary Pharmacology and Therapeutics 23: 251-260.
'Intratracheal clenbuterol in the horse: its pharmacological efficacy and analytical detection ' () 23 Journal of Veterinary Pharmacology and Therapeutics : 251 -260 .
-
Helsel, D.R., 2012. Statistics for censored environmental data using Minitab and R. Vol. 77. John Wiley and Sons, Hoboken, NJ, USA.
'Statistics for censored environmental data using Minitab and R. Vol. 77 ', ().
-
Jambhekar, S.S. and Breen, P.J., 2012. Extravascular routes of drug administration. In: Foster, R.W. (ed.) Basic pharmacology, 2nd edition. Butterworths, London, UK, pp. 105-126.
'Extravascular routes of drug administration ', () 105 -126 .
-
Kane, R.A., Fisher, M., Parrett, D. and Lawrence, L.M., 1987. Estimating fatness in horses. In: Proceedings of the 10th Equine Nutrition and Physiology Symposium, Fort Collins, CO, USA, pp. 127-131.
Estimating fatness in horses 127 131
-
Kearns, C.F. and McKeever, K.H., 2002. Clenbuterol diminishes aerobic performance in horses. Medicine and Science in Sports and Exercise 34: 1976-1985. https://doi.org/10.1249/01.MSS.0000038973.96796.1E.
-
Kearns, C.F., McKeever, K.H., Malinowski, K., Struck, M.B. and Abe, T., 2001. Chronic administration of therapeutic levels of clenbuterol acts as a repartitioning agent. Journal of Applied Physiology 91: 2064-2070. https://doi.org/10.1152/jappl.2001.91.5.2064.
-
Khazaeinia, T., Ramsey, A.A. and Tam, Y.K., 2000. The effects of exercise on the pharmacokinetics of drugs. Journal of Pharmaceutical Sciences 3: 292-302.
'The effects of exercise on the pharmacokinetics of drugs ' () 3 Journal of Pharmaceutical Sciences : 292 -302 .
-
Knych, H.K., Harrison, L.M., Steinmetz, S.J., Chouicha, N. and Kass, P.H., 2016. Differential expression of skeletal muscle genes following administration of clenbuterol to exercised horses. BMC Genomics 17: 596. https://doi.org/10.1186/s12864-016-2945-2
-
Lehner, A.F., Harkins, J.D., Karpiesiuk, W., Woods, W.E., Robinson, N.E., Dirikolu, L., Fisher, M. and Tobin, T., 2001. Clenbuterol in the horse: confirmation and quantitation of serum clenbuterol by LC-MS-MS after oral and intratracheal administration. Journal of Analytical Toxicology 25: 280-287.
'Clenbuterol in the horse: confirmation and quantitation of serum clenbuterol by LC-MS-MS after oral and intratracheal administration ' () 25 Journal of Analytical Toxicology : 280 -287 .
-
Machin, J., Duer, W., Maylin, G., Fenger, C., Wilson, D., Ivey, M., Berthold, B., Allison, S. and Tobin, T., 2019. Variability in plasma concentrations of methylprednisolone 6 days after intrasynovial injection of methylprednisolone acetate in racing horses: a field study. Equine Veterinary Journal 51: 343-348.
'Variability in plasma concentrations of methylprednisolone 6 days after intrasynovial injection of methylprednisolone acetate in racing horses: a field study ' () 51 Equine Veterinary Journal : 343 -348 .
-
Milano, G., Chiappini, S., Mattioli, F., Martelli, A. and Schifano, F., 2018. β-2 agonists as misusing drugs? Assessment of both clenbuterol- and salbutamol-related European Medicines Agency (EMA) pharmacovigilance database reports. Basic and Clinical Pharmacology and Toxicology 123:182-187.
'β-2 agonists as misusing drugs? Assessment of both clenbuterol- and salbutamol-related European Medicines Agency (EMA) pharmacovigilance database reports ' () 123 Basic and Clinical Pharmacology and Toxicology : 182 -187 .
-
Millerick-May, M.L., Karmaus, W., Derksen, F.J., Berthold, B., Holcombe, S.J. and Robinson, N.E., 2011. Particle mapping in stables at an American Thoroughbred racetrack. Equine Veterinary Journal 43: 599-607.
'Particle mapping in stables at an American Thoroughbred racetrack ' () 43 Equine Veterinary Journal : 599 -607 .
-
Nolen-Walston, R.D., Moore, C.M., Barr, C.A., Tomlinson, J.E., Boston, R.C. and Soma, L.R., 2015. Effect of long-term oral administration of a low dosage of clenbuterol on body fat percentage in working and nonworking adult horses. American Journal of Veterinary Research 76: 460-466. https://doi.org/10.2460/ajvr.76.5.460
-
Owen, D.B., 1968. Survey of properties and applications of the non-central t-distribution. Technometrics 10: 445-478.
'Survey of properties and applications of the non-central t-distribution ' () 10 Technometrics : 445 -478 .
-
Sasse, H.H. and Hajer, R., 1977. Veterinary and clinical experience of the use of a beta2-receptor-stimulating sympathicomimetic agent (NAB 365) in horses with respiratory disease. Tijdschrift voor Diergeneeskunde 102: 1233-1238.
'Veterinary and clinical experience of the use of a beta2-receptor-stimulating sympathicomimetic agent (NAB 365) in horses with respiratory disease ' () 102 Tijdschrift voor Diergeneeskunde : 1233 -1238 .
-
Savage, I.R., 1961. Probability inequalities of the Tchebycheff type. Journal of Research of the National Bureau of Standards – B. Mathematics and Mathematical Physics B 65: 211-222.
'Probability inequalities of the Tchebycheff type ' () 65 Mathematics and Mathematical Physics B : 211 -222 .
-
Sleeper, M.M., Kearns, C.F. and McKeever, K.H., 2002. Chronic clenbuterol administration negatively alters cardiac function. Medicine and Science in Sports and Exercise 34: 643-650.
'Chronic clenbuterol administration negatively alters cardiac function ' () 34 Medicine and Science in Sports and Exercise : 643 -650 .
-
Soma, L.R., Uboh, C.E., Guan, F., Moate, P., Luo, Y., Teleis, D., Li, R, Birks, E.K., Rudy, J.A. and Tsang, D.S., 2004. Pharmacokinetics and disposition of clenbuterol in the horse. Journal of Veterinary Pharmacology and Therapeutics 27: 71-77.
'Pharmacokinetics and disposition of clenbuterol in the horse ' () 27 Journal of Veterinary Pharmacology and Therapeutics : 71 -77 .
-
Thompson, J.A., Mirza, M.H., Barker, S.A., Morgan, T.W., Bauer, R.W. and McConnico, R.S., 2011. Clenbuterol toxicosis in three Quarter Horse racehorses after administration of a compounded product. Journal of the American Veterinary Medical Association 239: 842-849.
'Clenbuterol toxicosis in three Quarter Horse racehorses after administration of a compounded product ' () 239 Journal of the American Veterinary Medical Association : 842 -849 .
-
Turgut, K. and Sasse, H.H., 1989. Influence of clenbuterol on mucociliary transport in healthy horses and horses with chronic obstructive pulmonary disease. Veterinary Record 125: 526-530.
'Influence of clenbuterol on mucociliary transport in healthy horses and horses with chronic obstructive pulmonary disease ' () 125 Veterinary Record : 526 -530 .
-
US Anti-Doping Agengy (USADA), 2019. Clenbuterol and meat contamination. Available at: https://tinyurl.com/yxlhgsxm
-
Wilsher, S., Allen, W.R. and Wood, J.L.N., 2006. Factors associated with failure of Thoroughbred horses to train and race. Equine Veterinary Journal 38: 113-118.
'Factors associated with failure of Thoroughbred horses to train and race ' () 38 Equine Veterinary Journal : 113 -118 .
-
Wood, J.L.N., Newton, J.R., Chanter, N. and Mumford, J.A., 2005. Association between respiratory disease and bacterial and viral infections in British racehorses. Journal of Clinical Microbiology 43: 120-126.
'Association between respiratory disease and bacterial and viral infections in British racehorses ' () 43 Journal of Clinical Microbiology : 120 -126 .
| All Time | Past 365 days | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 0 | 0 | 0 |
| Full Text Views | 71 | 53 | 2 |
| PDF Views & Downloads | 82 | 70 | 1 |
Clenbuterol plasma concentrations after therapeutic administration in fit Standardbred horses: threshold recommendations
In: Comparative Exercise PhysiologySearch for other papers by K.H. McKeever in
Current site
Google Scholar
PubMed
Search for other papers by H.C. Manso Filho in
Current site
Google Scholar
PubMed
Search for other papers by E.M. Rankins in
Current site
Google Scholar
PubMed
Search for other papers by C.S. Duchamp in
Current site
Google Scholar
PubMed
Search for other papers by Y. Salah in
Current site
Google Scholar
PubMed
Search for other papers by C.K. Fenger in
Current site
Google Scholar
PubMed
Search for other papers by W.C. Duer in
Current site
Google Scholar
PubMed
Search for other papers by K. Malinowski in
Current site
Google Scholar
PubMed
Search for other papers by G.A. Maylin in
Current site
Google Scholar
PubMed
Clenbuterol, (RS)-1-(4-amino-3,5-dichlorophenyl)-2-(tert-butylamino)ethan-1-ol, as Ventipulmin is an FDA approved β2 agonist medication for the management of airway obstruction in horses. Administration above the FDA approved doses for clenbuterol produces repartitioning effects, which have led to restrictions on its use in human athletics and Quarter Horse and Thoroughbred racing. Clenbuterol, however has long been used therapeutically at FDA approved doses in Harness racing. The goal of this study was to identify a withdrawal time guideline for its use at FDA approvsed dose levels in Harness racing, where horses may start at seven-day intervals. Eight healthy, moderately fit Standardbred horses (4 mares, 4 geldings, weight 491±40 kg, age 13±2 years) were administered 0.8 μg/kg of clenbuterol as Ventipulmin syrup twice daily (BID) for three days. Blood samples were collected prior to dosing and at 1, 24, 48 and 96 h post administration. Clenbuterol was quantified in all samples using the New York Drug Testing and Research Laboratory ISO-17025 Racing and Medication Testing Consortium (RMTC) accredited quantitative procedure. The lower limit of quantitation of the method was 1.0 pg/ml, and three data points at 96 h post administration were censored. One horse developed diarrhoea and data from this horse was excluded from the overall analysis. Plasma regulatory thresholds were calculated using the 95/95 tolerance method and Gauss Camp Meidell at P=0.05 and P=0.001. Horses were also evaluated for effects of clenbuterol on body composition using body mass and ultrasound measurements of rump fat thickness. There were no effects (P>0.05) of clenbuterol on any of the measures including fat mass and fat free mass and thus no repartitioning effect was observed. The pharmacokinetic data and the 96 h data set support the therapeutic use of clenbuterol in Harness horses at the FDA approved 0.8 μg/kg BID dose for three days and suggest a 41 pg/ml regulatory threshold for a 96 h withdrawal time with a P=0.001 probability of randomly exceeding this regulatory threshold.
| All Time | Past 365 days | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 0 | 0 | 0 |
| Full Text Views | 71 | 53 | 2 |
| PDF Views & Downloads | 82 | 70 | 1 |