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EQUINE VETERINARY EDUCATION / AE / MARCH 2016
Original Article
Clearance of corticosteroids following intra-articular administration of clinical doses to racehorses
H. K. Knych*†‡, J. A. Blea§, R. M. Arthur¶, L. R. Overly†† and C. W. McIlwraith‡‡ †K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, USA; ‡Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, USA; §Von Bluecher Blea Hunkin Inc., Sierra Madre, California, USA; ¶School of Veterinary
Medicine, University of California, Davis, USA; ††Equine Sports Medicine LRO Inc, Cypress, California, USA; and ‡‡Equine Orthopaedic Research Center, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, USA. *Corresponding author email:
hkknych@ucdavis.edu
Keywords: horse; corticosteroid; intra-articular; horse racing; clearance
Summary Over the last few years there has been a nationwide cooperative effort to establish threshold concentrations and withdrawal time guidelines for corticosteroid use in racehorses. As dosing regimens are specific to individual horses and highly variable, it is not possible to establish regulatory guidelines for every dosing scenario and therefore they are often based on single dose administration studies. The goal of the study described here was to assess the applicability of current regulatory recommendations for intra- articular corticosteroids based on clinical protocols used by practitioners. A total of 58 Thoroughbred and 82 Quarter Horse racehorses received varying doses of triamcinolone acetonide, methylprednisolone acetate, isoflupredone or betamethasone intra-articularly in various joints by the treating practitioner. Blood samples were collected at 0, 7, 10, 14, 21, 28 and 35 days post drug administration and serum samples analysed by liquid chromatography mass spectrometry for quantitation of drug concentrations. Serum elimination varied depending upon the dose and the number and specific joints treated. Serum concentrations fell below the ARCI threshold guidance by Day 7 (100 pg/ml) for both triamcinolone acetonide (2–40 mg dose) and isoflupredone acetate (4– 30 mg dose) and Day 21 (100 pg/ml) for methylprednisolone acetate (20–600 mg dose). Betamethasone fell below the regulatory threshold (10 pg/ml) by 7 days for all Quarter Horses and for 7/10 Thoroughbreds studied. Drug concentrations were below the regulatory threshold by Day 10 in the remaining 3 horses receiving betamethasone.
Introduction
The goal of a medication control programme is to: 1) assure the health and welfare of animal and human participants, 2) assure a fair and level playing field for all competitors and 3) safeguard the public interest with anti-doping regulations wherever sanctioned wagering is involved. Over the last few years, there has been an international effort to address the use of therapeutic medications commonly used in racing, including corticosteroids. Historically, regulation of horse racing in the United States (US) was on a state-by-state basis and it was up to specific jurisdictions to establish regulatory recommendations. Additionally, most regulations were established well before simulcasting and interstate wagering
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was legal. In spite of sporadic efforts at uniformity over the last several years, there were considerable variations between state medication and drug regulations and how those regulations are administered. In 2001, a meeting of national industry stakeholders, sponsored by the American Association of Equine Practitioners, led to the establishment of the Racing Medication and Testing Consortium (RMTC). The RMTC was tasked with promoting national uniformity with respect to medication regulations. The result has been a cooperative effort within the racehorse industry to develop a national uniform medication programme (NUMP) by establishing regulatory thresholds and withdrawal time guidance for a limited number of therapeutic medications. Whenever feasible, the preference in the US is to regulate therapeutic medications in blood (serum or plasma). This effort has been spearheaded by the RMTC through drug administration research and subsequent recommendations to the Association of Racing Commissioners International (ARCI). The ARCI represents the majority of the 38 separate racing authorities in the US and maintains the Model Rules for racing in the US (ARCI Model Rules,
https://ua-rtip.org/industry_ service/download_model_rules). All states in which racing occurs are encouraged, but not required, to adopt the Model Rules. Corticosteroids are potent anti-inflammatory agents and,
as such, are commonly used to treat performance-related musculoskeletal injuries and other inflammatory conditions in equine athletes. In the US, they are currently classified by the ARCI as Class 4 foreign substances with a penalty category C (ARCI Model Rules). Due to their potent anti-inflammatory effects, corticosteroid use close to competition is of particular concern to regulatory authorities because of the potential to mask injuries that may otherwise keep a horse from racing. Regulatory thresholds and withdrawal time guidance are typically based on carefully controlled studies, utilising a single dose commonly used by veterinary practitioners. While necessary for establishment of regulatory guidance, this type of study does not necessarily reflect how corticosteroid drugs are typically used in clinical racecourse practice. In the case of corticosteroids, selection of a ‘common dose’ becomes more problematic, as the use pattern of this class of drugs is highly variable between practitioners (Ferris et al. 2011). Current NUMP regulatory thresholds for triamcinolone acetonide (TCA) and methylprednisolone acetate (MPA) are
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