This collection of monographs produced by the Racing Medication and Testing Consortium (RMTC) provides basic information on the medications on the Schedule of Controlled Therapeutic Substances (CTS). The goals of each monograph are:
- to provide equine veterinarians with information that allowed for effective treatment of their patients while maintaining compliance with medication regulations and
- to provide racing regulators with an overview of the medication – why and how it is used. The monographs demonstrate the relationship between the results of administration studies and the regulatory thresholds and withdrawal guidance derived from them; and educate on how withdrawal times and thresholds are determined.
Why Regulate Medication?
The RMTC medication regulation philosophy is based on three principles:
- Racehorses must be allowed to receive ethical and humane care;
- Only sound, healthy horses should be placed into competition; and
- Medication must not affect the outcome of a race.
The most important of these goals is horse and rider/driver safety. Limiting the presence of medications in racing horses can have a profound effect on safety overall. As an example, the use of non-steroidal anti-inflammatory drugs (NSAIDs) or local anesthetics in relative proximity to a race can alter a horse’s clinical presentation such that the examining veterinarian, the jockey or driver, and the horse itself, are unable to recognize the presence of orthopedic disease representing substantially increased risk for fatal fracture.
Other medications such as antihistamines, diuretics, and skeletal muscle relaxants may have less profound physiological effects in racing but still have the potential to impact the outcome of a race. For these, medication regulations protect the integrity of competition for horse owners and the wagering public. Scientifically derived thresholds also promote uniformity in medication regulation across multiple racing jurisdictions providing much needed consistency to industry participants and the wagering public.
How are Thresholds Developed?
In developing thresholds and withdrawal guidance, the RMTC performs a statistical calculation, the 95/95 Tolerance Interval. Also utilized by the FDA, Tolerance Interval Tests develop a standard that can be applied to a large population by using a limited number of test subjects. The use of drug administration studies and the 95/95 Tolerance Interval calculation allows for more reliable withdrawal guidance than the method used in many other countries where regulators rely on mathematical calculations, but do not actually administer the medication to horses. Alternatively, they perform administration studies involving 4-6 horses and disclose the number of days following the administration that the concentration of the medication in the study horses took to fall below an unpublished threshold. This interval, known as the Detection Time, requires that the practicing veterinarian make a determination for a withdrawal interval that is based on the detection time PLUS additional time, determined by the veterinarian, as a safety margin.
What Types of Studies are Used?
The RMTC uses limited pharmacokinetic (PK) studies. These administration studies examine a single medication at a specified dose, route of administration and treatment schedule.
The studies are conducted to make a threshold determination after the RMTC Scientific Advisory Committee (SAC) has made a philosophical determination for a withdrawal interval. The philosophical determinations are made with the guidance of the American Association of Equine Practitioners (AAEP) member racetrack veterinarians, the AAEP Racing Committee, and medication surveys. Additionally, for each medication the RMTC SAC considers the following:
- Ethical indications for use of the medication;
- The risk posed by the medication;
- Legitimate versus illicit use;
- Implications for equine welfare;
- The availability of FDA approved products for the horse;
- The availability of FDA approved products for other species;
- Any potential effect on athletic performance;
- The ARCI penalty classification;
- All existing threshold/withdrawal guidelines for similar medications; and
- RMTC’s medication philosophy for the specific substance.
After a medication has been selected for an administration study the SAC consults the AAEP Racing Committee, the manufacturer’s label instructions, veterinary clinical journals/ texts, veterinary pharmacologists, Internal Medicine Specialists, and practicing racetrack veterinarians to determine appropriate study dose, route of administration, dosing frequency, and duration of treatment.
After a decision is made on an appropriate withdrawal interval, a limited PK study will provide results targeted at that interval and allow for the statistical calculation of a corresponding regulatory threshold. PK studies are designed to establish what the horse does to a medication by determining its absorption, distribution, metabolism, and elimination over a period of time. The in-depth pre-study analysis, discussed above, allows the use of PK studies that focus on a specified interval post-administration.
The use of Tolerance Interval calculations to develop threshold recommendations, permits the use of limited studies that can accurately track the elimination of a single medication over time. In these studies, all test horses are exposed to the same management program thereby reducing the number of variables that could impact study results. The resulting data acquired from samples collected at a specific time point is subjected to the Tolerance Interval Test calculation. The result of that calculation, that includes a correction for variability that would be expected to occur outside of the limited study, can be applied with confidence to the vast population of racehorses.
Conversely, population studies include horses managed under a spectrum of training regimens, feeding programs, husbandry practices, and potentially receiving other medications in addition to the one selected for study. These multiple, uncontrolled variables can confound study results and make it difficult to establish reliable withdrawal guidance or regulatory thresholds. Population studies require many more horses for statistical relevance.
The results of PK studies are specific to dose, route of administration, frequency of administration, duration of treatment, and in some cases injection site. It is important to note that administration of a medication at a different dosage, route of administration, administration site, or number of doses may change the needed withdrawal time. Medications that are administered over time in multiple doses may need additional withdrawal time to fall below threshold levels. Veterinarians are advised to use caution when altering the method or dose of any medication and consider a longer withdrawal period.
Additionally, since some medications can affect the elimination of others it is important to adjust withdrawal times accordingly if administering multiple medications. Clearance testing, to ensure that the concentration of the medication is below the regulatory threshold before the horse is entered to race, is advisable when medications are co-administered, a medication administration does not conform to the protocol used to establish withdrawal guidance, or when warranted by the health status of an individual horse.
Another type of research, the pharmacodynamics (PD) study, attempts to establish what effect(s) a medication has on the horse. This work is substantially more complex as not only must the intended effect of a medication be measured, but secondary or side-effects must also be considered. It is possible that a side-effect may have greater implications for impacting racing performance than the intended effect. An example of this would be that many antihistamines having a primary effect of relieving allergy symptoms are also associated with the side-effect of drowsiness. Even where these studies are performed it is difficult to develop statistically significant data that can differentiate the performance impacting effect of a medication in a sport where fractions of a second can mean the difference between first and second place. Because of the limited value of this information, pharmacodynamic studies are not often pursued for the purposes of developing thresholds and withdrawal guidance.
Conclusion
This collection of monographs is not a formulary for dosing and withdrawal of the listed medication in all situations or horses. It is intended to be a tool to help veterinarians gain familiarity with thresholds and withdrawal times in the context of providing ethical and humane care to their patients.
The use of compounded medications represents another risk of unknown extent as these substances are produced absent regulatory oversight, and the concentration of drug, its stability and purity, have not been independently verified.
The RMTC advises all veterinarians to use these findings as guidelines; they are not intended as guarantees of regulatory compliance. Rather they should be used as a foundation for establishing a withdrawal interval in consideration of specific knowledge of the horse’s health, management, fitness, and treatment protocol. The RMTC cautions veterinarians and trainers that exact repetition of these medication dosages may still lead to levels above the threshold concentration. Where questions exist, the RMTC recommends clearance testing for horses prior to entry.
