The University of Kentucky hosted the first session of its 10th annual Equine Research Showcase in a virtual setting Jan. 5.

Scott Stanley, PhD, professor of analytical chemistry at the UK Gluck Equine Research Center kicked off the series and the evening’s session with a talk on therapeutic medication usage in performance horses, with a focus on bisphosphonates, non-steroidal anti-inflammatory drugs (NSAIDS) and other medicines in the juvenile horse.

Outlining the steps for drug detection in racing, Stanley provided viewers a background about what drugs are used, how much is allowed and what type of horses could use them in a given situation. Stanley also covered new Kentucky guidelines for drug use.

“Horse racing has the longest established, most elaborate, broad-based and technically-accurate systems for drug detection of any competitive sport,” Stanley said. 

According to Stanley, there are four key parts of a horse drug testing program. What are you looking for? Where are you going to look for it? How are you going to find it? What does it mean?

Stanley explained that in order to test for substances in horses, testers search for anything not specifically allowed. Only authorized medications may be administered after entering a race, like a NSAID (phenylbutazone) or Salix® (furosemide), yet the rules for these have changed over the course of the past couple of years. Urine and plasma thresholds are also monitored for some therapeutic drugs, and the United States Equestrian Federation’s list of prohibited substances (stimulants, depressants, tranquilizers and anesthetics) are looked for as well.

When defining where to look for prohibited substances in a horse’s system, Stanley said that the performance horse industry frequently uses screened urine samples. This is because most drugs are concentrated and eliminated in the urine and urine samples are relatively easy to obtain. He cautioned, however, that the concentration of a drug in the urine does not correlate well with the effect of the drug in the system.

According to Stanley, another way of testing for illicit substances in a horse is through blood sampling, which he said is the more frequently used test for threshold medications. The concentration of the drug found within the blood screening can be more accurately correlated to the effect of the drug in the system. Other samples like saliva, hair and various tissue samples (liver, kidneys, joint fluid and bone) can also be used for testing.

What does this mean?

Stanley said that for many years, those conducting tests either didn’t pay enough attention to the significance of their findings or their testing wasn’t sensitive enough to determine concentrations that had no relevance.

“We do have situations where concentration may affect the horse’s appearance or performance, and we need to know when that concentration is no longer present and whether a small amount of therapeutic medication should be allowed as a threshold,” Stanley said.

Stanley said one of the most frequent questions he gets from veterinarians is about withdrawal timeframes.

“More times than not, those questions come about with a veterinarian already having formulated an answer, but they want to verify that since the horse is in a competition,” Stanley said. 

According to Stanley, there are many factors that affect withdrawal times, including the dose, frequency of drug administration, route of drug administration and the drug preparation (e.g. slow release).

With regard to bisphosphonates, Stanley said that they have been approved for use in horses for the last several years but have been around for approximately the past 50.

“Bisphosphonates have been used in human medicine for over 20 years, but they’ve only been licensed in veterinary medicines since 2014,” Stanley said.

He described bisphosphonates as “bone drugs,” the term coined since they interfere with osteoclast activity (inhibit bone resorption).

“The intention is, if we inhibit bone resorption, we get more bone mass added overall,” he said.

He explained to viewers that bisphosphonates are synthetic analogues of inorganic pyrophosphate and contain a phosphate-carbon-phosphate backbone. The potency of the bisphosphonates is determined by the carbon sidechains on the chemical structure.

According to Stanley, there are two classes of bisphosphonates typically used, the amino or nitrogen containing class and the non-amino containing class. The non-nitrogen containing bisphosphonates are the ones that are approved for veterinary medicine, and the amino-containing class is commonly used in human medicine.

The two bisphosphonates mentioned by Stanley include the clodronate disodium Osphos® (Dechra) and Tildronate disodium Tildren®(Bimeda). These are licensed and approved for use in the horse for navicular disease. They vary in routes of administration; Osphos® is administered intramuscularly and Tildren® is administered intravenously.

Stanley said there aren’t very many studies done to describe how these bisphosphonates work in the horse, what they actually work on and how effective they are. He did point to some studies reviewed on Tildren® from 2007 and 2008 that looked at bone resorption markers.

“These studies did show decreases in biomarker CTX-1, and that was fairly short-lived. They didn’t show any histology, and the bone density changes were very difficult to monitor,” he said.

The uses of bisphosphonates that have been established as treatments in juvenile horses are disease-associated with the subchondral bone of the fetlock and carpus; osteo-articular pain in any location; pain arising from the thoracolumbar (back) and pelvic regions; prevention and treatment of stress fractures; to improve the action of “poor movers;” and general fetlock pain “when all else fails.”

According to Stanley, significant risks can come with these uses.

“They can and may change the mechanism of action for bone maintenance and remodel. The accumulation of microfractures then may, in fact, leave the bone more fragile,” he said. “The turnover of bone matrix is also affected, and the increase turnover would lead to bone fragility as well. There may be a delayed healing process; the damaged cartilage may accelerate bone and joint degeneration; and the potential for the analgesic component may disguise the signs of a more serious injury.”

He clarified that the analgesic (drug classification that relieves pain) component is not well documented, but many veterinarians feel that they get an analgesic component for at least 10 days or longer after treatment with bisphosphonates.

Stanley also covered the Kentucky Horse Racing Commission Bisphosphonate Policy. The policy states that a horse under 4 years old shall not be administered a bisphosphonate. If the horse is found to have been administered a bisphosphonate, it will result in disqualification from competition or potentially the reversal of a sale. In addition, the horse would be placed on the Veterinarian’s List for a minimum of six months from date of sampling. Horses 4 years and older can be administered a bisphosphonate, providing it has been FDA approved, administered in accordance to label requirements, is for navicular disease and is administered by a licensed veterinarian. These horses are also be placed on the Veterinarian’s List for a minimum of six months after the last administration.    

Stanley also touched on NSAIDs and their widely monitored uses in the juvenile horse. The Racing Medication and Testing Consortium’s (RMTC) current guidelines for the NSAID phenylbutazone recommends a 48-hour treatment window with a maximum dose of 2 grams intravenously.

“There’s also a recommendation for a secondary withdrawal guideline, the minimum recommendation as a secondary nonsteroidal is now seven days. In order to avoid violation by the stacking rule, you would have to have a seven-day withdrawal of phenylbutazone if you wanted to use flunixin or ketoprofen at 48 hours,” Stanley said.

Like phenylbutazone, if flunixin is the primary drug being administered, there is also a 48-hour treatment guideline. If flunixin is used as a secondary drug, though, it has a six-day withdrawal guideline to stay in compliance with the stacking rule. Ketoprofen, less frequently used, can also be used in the same way, but as a secondary drug it requires a four-day withdrawal to stay in compliance with the stacking rule.

Stanley also briefly touched on the furosemide regulation change. The RMTC lists furosemide still as “per the regulation of 1.010 urine specific gravity and 100 nanograms per ml of furosemide threshold, and the recommended dose being 500 mg and minimum of 150 mg I.V., four hours before racing.”

New regulations in Kentucky and many other jurisdictions are looking at the withdrawal of furosemide within 24 hours.

“The rule currently says that no medication shall be administered of any kind, including furosemide, within 24 hours of post-time,” Stanley said.

These are the new rules for Kentucky that went into effect Jan. 1, 2020, for all 2-year-olds and on Jan. 1, 2021, for all horses entered in a stakes race. The rule specifies that these horses shall not be administered any drug, medication or substance including furosemide, within 24 hours of post-time. To regulated this, the threshold concentration of furosemide is 1.0 nanograms per ml in serum in a post-race sample.

Sabrina Jacobs, a senior majoring in equine science and management and minoring in wildlife biology and management, is a communications and student relations intern with UK Ag Equine Programs.