Dr. Heather Knych | Horse Racing Free Tips

HISA’s Lasix Advisory Committee Set

Edited Press Release

The Horseracing Integrity and Safety Authority (HISA) announced the members of an Advisory Committee which has been convened to oversee a three-year study on the use of furosemide (also known as “Lasix”) on horses during the 48-hour period before the start of a Covered Horserace, including the effect on equine health and the integrity of competition.

The establishment of this Advisory Committee for the study of furosemide administration and the requirements of the study are specifically mandated and set forth in the Horseracing Integrity and Safety Act. The HISA Board of Directors delegated its authority to select the Advisory Committee members to HISA's Anti-Doping and Medication Control (ADMC) Committee who did so based on the members' relevant expertise. The Advisory Committee will oversee the process of issuing a Request for Proposal to conduct the research, reviewing grant applications from academic researchers and allocating grant funding for the study.

When the independent scientific research has been completed and published, it will be presented to the Advisory Committee who will then relay the findings and their recommendations to the HISA Board of Directors.

The Furosemide Advisory Committee is comprised of the following members:

Emma Adam, DVM, Ph.D., is a veterinarian with over 24 years of racing experience in the United States, United Kingdom, France and Australia. She is board-certified in equine medicine from Texas A&M University and in surgery from the New Bolton Center at the University of Pennsylvania. Dr. Adam also received her Ph.D. in musculoskeletal science from the University of Kentucky's Gluck Equine Research Center.
Alan Foreman is Chairman of the Thoroughbred Horsemen's Association (THA) and Vice-Chairman of the Racing Medication and Testing Consortium (RMTC). Foreman is considered one of the leading racing law and equine attorneys in the United States and is an expert on medications used in horse racing.
Scott Hay, DVM, is a veterinarian at Teigland, Franklin and Brokken, where he focuses on lameness, performance evaluations and purchase examinations. He also serves on the RMTC's Scientific Advisory Committee. Dr. Hay previously served as President of the American Association of Equine Practitioners (AAEP) and as a member of the Grayson-Jockey Club's Scientific Advisory Committee.
Ted Hill, VMD, is a racing steward for The Jockey Club with more than 23 years of experience. He previously served as Chief Veterinarian for the New York Racing Association (NYRA). Dr. Hill received his VMD from the University of Pennsylvania.
Rob Holland, DVM, Ph.D., is a respiratory and infectious disease specialist in Lexington, Kentucky and partner at Holland Management Services, Inc., a consulting practice offering solutions in outcomes research and veterinary medicine. Dr. Holland has worked with the Kentucky Horse Racing Commission (KHRC) and is an expert in equine drug testing processes.
Heather Knych, DVM, Ph.D., DACVCP, is a Professor of Clinical Veterinary Pharmacology and Head of the Pharmacology Section at the K.L. Maddy Equine Analytical Chemistry Pharmacology Laboratory at the School of Veterinary Medicine at the University of California, Davis. Dr. Kynch is board-certified in Clinical Veterinary Pharmacology and has an extensive publication record in the areas of pharmacokinetics and pharmacodynamics. She received her DVM and Ph.D. in Pharmacology and Toxicology from the University of California, Davis, where she also conducted her residency in Veterinary Pharmacology.
Ryan Murphy is the Executive Director for the Partnership for Clean Competition (PCC), the leading anti-doping research organization dedicated to the protection of clean athletes. Prior to joining the PCC, Murphy served as Program Officer with the Sports Diplomacy division at the U.S. Department of State and prior to that as Senior Manager for Sport & Competition for Special Olympics International. Murphy has also worked as an International Doping Control Officer for International Doping Tests & Management. In addition to his work at the PCC, Murphy serves as an Adjunct Professor for the Sports Industry Management Master's program at Georgetown University.
Foster Northrop, DVM, is a practicing racetrack veterinarian with more than 35 years of industry experience. He has served on the boards of the KHRC and American Veterinary Medical Association (AVMA), as well as the RMTC's Scientific Advisory Committee.
Scott Palmer, VMD, is a former President of the AAEP and the American Board of Veterinary Practitioners (ABVP). He also chaired the New York Task Force for Racehorse Health and Safety from 2011 to 2013 and served as a clinician and referral surgeon at the New Jersey Equine Clinic for 38 years. He is currently a member of the RMTC's Scientific Advisory Committee, the Horseracing Testing Laboratory Committee, the Association of Racing Commissioners International's (ARCI) Drug Testing and Standards Committee and the ARCI's Equine Welfare and Veterinarians Committee.
N. Edward Robinson, BVetMed, Ph.D., is a nationally recognized veterinarian, academic and researcher who spent nearly 50 years at Michigan State University's College of Veterinary Medicine, during which he spent more than 20 years as the Matilda R. Wilson Professor of Large Animal Clinical Sciences. Dr. Robinson has spent his career researching lung disease in horses. He received his veterinary degree from the Royal Veterinary College in London and a Ph.D. from University of California, Davis.
Corinne Sweeney, DVM (HIWU Appointment), is an American College of Veterinary Internal Medicine (ACVIM) specialist and has spent the past 44 years at the University of Pennsylvania School of Veterinary Medicine. She has served as a member of the Pennsylvania State Horse Racing Commission since 2008 and previously served as Chair of the ARCI in 2019. She is a certified Organizational Ombuds Practitioner and has served as the Penn Vet Ombuds since 2015.

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Getting Down to the Science of It All In Medina Spirit DQ Appeal

FRANKFORT, KY – After a brief private meeting between attorneys and the hearing officer to discuss “confidentiality” matters, the Kentucky Horse Racing Commission's hearing addressing trainer Bob Baffert's appeal continued, slowly but surely, on Wednesday in Frankfort, KY.

While Tuesday's session focused on the KHRC's medication rules, along with those established by the industry's Racing Medication and Testing Consortium (RMTC) and the model rules of the Association of Racing Commissioners International (ARCI), the center of interest Wednesday was the corticosteroid betamethasone itself.

The day started off with Dr. Heather Knych, a professor of clinical veterinary pharmacology and head of the pharmacology section at the K.L. Maddy Equine Analytical Pharmacology Laboratory at the School of Veterinary Medicine at the University California, Davis. She provided her testimony via Zoom (from California) as an expert witness.

Called to the stand (virtually) by KHRC general counsel Jennifer Wolsing, Knych spoke to her area of specialty in equine pharmacology, with special interests specifically in studying drug metabolism, anti-inflammatory drugs, pain management and emerging threats. Knych explained that she has studied the effects of drugs on performance horses for nearly 15 years and has had several studies focused on corticosteroids published.

Wolsing asked Knych to explain what betamethasone is, what the effects of it are, and made note of the longevity of its effects in a genomic sense. Along that line of questioning, the KHRC's Medication Classification Schedule was pulled up as an exhibit, as Knych was asked if she agreed with betamethasone being listed as a Class C medication.

“I agree with its classification as a Class C medication. Based on the description, it's an FDA approved drug, it's a therapeutic agent and it has moderate potential to affect performance. [It] could potentially mask a lameness or injury and fits nicely with the other medications in this category,” said Knych, who also serves on the RMTC's Scientific Advisory Committee.

When asked if the administration of the drug matters in terms of measuring its impact, she replied, “I don't think it matters. The drug is the drug. Once it gets in the system, that's what we're looking at, [what it does] once it gets in the body and its effect.”

Diving deeper into the specifics of betamethasone and corticosteroids in general, Knych discussed the effects of various cortisol levels, how that is measured, and the overall picture when it comes to how the concentration of a drug in the horse's system correlates directly with the effects of the drug. Wolsing presented various published studies on the topics at hand during this time, including some that Knych was involved with herself. Some of the studies focused on betamethasone, while others centered around the effects of dexamethasone, a comparable drug that is also listed as a Class C medication.

When asked if the health and safety of the horse is part of the focus in equine pharmacology work, Knych said, “The primary reason corticosteroids are so tightly regulated is to eliminate the potential to affect performance, the potential to mask [things such as] lameness.”

Knych also acknowledged that there is potential of masking underlying health issues when using higher amounts of betamethasone.

However, when it came to the findings from the studies presented, Knych did say, “We don't know the end pharmacological effect of betamethasone in the horse.” She also said there have been no studies done specifically on the effects of betamethasone in horses when administered as a topical ointment.

During this time, Wolsing cited the KHRC's case with trainer Graham Motion in 2015, involving a stewards' ruling after a horse he trained that raced was found with too much methocarbamol in its system, to show that the commission has a right to regulate in situations where there is gray scientific area with regard to medication. Craig Robertson, an attorney for Baffert, argued against its relevance when discussing the systemic effects of corticosteroids.

Motion claimed he followed the RMTC guidelines for withdrawal but was still flagged, which is a similar claim from Baffert in terms of what happened with Medina Spirit's post-race result that revealed a betamethasone overage, which ultimately resulted in the colt's disqualification from his victory in the 2021 GI Kentucky Derby.

Robertson, who was part of the KHRC case involving Motion in 2015, believed the case was being mischaracterized and stated, “The case says that you have to have a rational scientific basis for what you do.”

Wolsing also asked Knych if the route of administration of the drug has any bearing on the effect of the drug once it is in the horse's system. She replied, “No. It depends on what the concentration of the drug is regardless. I'm talking about the concentrations at the end, when we still see suppression of cortisol.”

In one of her final inquiries, Wolsing stated, “Medina Spirit was administered approximately 45 milligrams of Otomax from a bottle over a period of about Apr. 9 and going through Apr. 30, the day before the [2021] Derby.” She followed up asking Knych what the impact of that would be on the horse.

“I don't think we can say one way or another. We don't have the science to say one way or another,” she replied.

Her response was met with audible satisfaction from Baffert's legal team, who took over from there, as they continued to argue that the KHRC's medication rules lack detail and scientific backing, specifically when it comes to administering betamethasone in the form of a topical ointment.

The cross-examination of Knych, conducted by Baffert's attorney Joe DeAngelis, delved into the inexactness of the science in the studies of and testing for betamethasone, along with how long it takes for betamethasone to leave a horse's system–intended to enforce that the 14-day withdrawal period established by the KHRC was unreliable.

The RMTC's Controlled Therapeutic Substances Monograph Series was also brought up, as DeAngelis asked if Knych recalled discussing or hearing any discussion about the ethics and safety of topical use of betamethasone. She said she hadn't. When asked if there had been any recommendation from the RMTC specifically on a stand-down period for topical use of corticosteroids, Knych replied, “No.”

DeAngelis also referenced RMTC's Position Statement on Corticosteroids, a study published in 2013, which showed that the use of topical corticosteroids was known to RMTC at the time the findings were published.

When asked if she approved of the 14-day stand-down period, Knych replied, “Yes,” and admitted she did not recall any discussion of recommending it to be longer.

Knych's time as a witness, which lasted nearly 3 1/2 hours, ended with some final questions from Wolsing and a few remaining questions for the sake of clarification from DeAngelis.

Wolsing asked, “Could a much higher concentration affect a horse's health and safety?”

“Potentially yes, but what those levels are, I don't think we necessarily know that yet,” said Knych.

After a 45-minute lunch break, members of the media were asked to leave the conference room as lawyers met behind closed doors to discuss what hearing officer Clay Patrick, a Frankfort attorney, called “proprietary information.”

The hearing addressing Baffert's appeal to get his already served 90-day suspension and a $7,500 fine removed from his record, along with reinstating Medina Spirit's victory in last year's Kentucky Derby, continues Thursday at 9 a.m. and is expected to roll over into next week, starting Monday, Aug. 29.

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Research Confirms Bisphosphonates Can Linger In Horses’ Bones For Years

Bisphosphonates continue to be a topic of concern in the racing world, most notably raised by a report of a positive test from John Salder trainee Flagstaff, but researchers are still learning about how to find and regulate the drugs in horses. Although two drugs, sold under the trade names Osphos and Tildren, were approved by the Food and Drug Administration for use in horses several years ago, research into the drugs' action in young horses and the length of its life inside the equine body is still catching up. (FDA-mandated testing is focused on safety and efficacy of a new drug, not necessarily the ability of a state racing commission to detect it in a post-race sample from a young racehorse.)

Read more about bisphosphonates in our archives here and here.

Dr. Heather Knych, renowned equine pharmacologist at the University of California-Davis, gave an overview of current research on bisphosphonates at the most recent, virtual convention of the American Association of Equine Practitioners (AAEP).

A few takeaways:

Bisphosphonates may be new to the horse world, where they are FDA-approved for the management of navicular syndrome in older horses, but the drug class has actually been in use in different settings for a couple of centuries. Knych explained that the substance was first used in the detergent industry in the 1800s as a water softener, anti-corrosive or anti-scaling agent. Their action on calcium carbonate made them effective in these settings. They were adapted as therapeutic drugs for human bone conditions in the 1970s.
While we've most often heard of bisphosphoantes in humans as part of osteoporosis treatment, they've also been used in metastatic bone disorders, and multiple myeloma.
We know that after an administration, bisphosphonates disappear from blood fairly quickly – their half life is one to two hours in plasma, but they can linger on bone surfaces for months or years.
Bisphosphonates seem to prefer settling in trabecular bone – bones like skulls and ribs that take less mechanical stress – over cortical bone, like the long bones in limbs. It withdraws from bones based on the amount of turnover in that bone, which can vary depending on age, exercise, and trauma.
Concentrations of bisphosphonates continues to increase as concentrations of it elsewhere decreases. It can also release from bone back into blood in small amounts and move into other bone surfaces, though we don't know a lot about why and when it does that.
Knych presented the results of a two-part study led by researchers across multiple universities to learn more about how long bisphosphonates linger in the skeleton. The first part of the project required administration of the two FDA-approved bisphosphonates – Osphos and Tildren – to a total of four horses in university research programs who were already slated for euthanasia for unrelated reasons. Bone samples were taken after euthanasia, which came four days or 30 days after administration in each drug group. Samples from the radial bones showed detectable amounts of both drugs four days after administration, with levels of Tildren being higher in both samples. Thirty days after administration, both drugs could be found in all bones sampled, even right and left molars. Concentrations of both drugs were highest in the tuber coxae (hips).
In the second phase of the study, researchers tested blood and fluid samples from four horses euthanized due to on-track injuries in California – three whose connections said they'd never had bisphosphonates, and one who had a treatment 18 months prior. The team could find no evidence of bisphosphonates in the three horses with no treatment history. The horse who had been treated 18 months before had no detectable amounts of the drug in serum, urine, or synovial fluid, but did have a detectable level in a sample from the radial bone.
These results suggest, in line with what veterinarians had expected based on human data, that the drug does linger on the surfaces of bone for considerable periods of time, and lives on different bones in different ways.
Knych acknowledged that both parts of the study came from extremely small sample sizes, as is often true in academic research with horses, and that further study is needed to better understand how bisphosphonates work in the equine body.

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Fact Check: The Pharmacology Of Betamethasone In Horses

It's clear that the battle over the outcome of the 2021 Kentucky Derby is likely to wage on for years to come. The Kentucky Horse Racing Commission (KHRC) has yet to make a ruling, but preliminary and split sample tests on winner Medina Spirit both came back positive for betamethasone in violation of Kentucky rules. Attorneys for Medina Spirit trainer Bob Baffert and owner Zedan Stables have been vocal about their feelings that the finding in the horse shouldn't matter for a variety of reasons — they say the administration of the drug to the horse came from a topical and not an injectable, they claim that post-race drug testing is designed to find therapeutic drugs at an unreasonably small concentrations, and they claim that the concentration found in Medina Spirit had no appreciable impact on the outcome of the race.

Further, Baffert attorney Craig Robertson said in a CNN interview June 3, a small amount of betamethasone detected in blood couldn't even be having an appreciable impact on the horse's body.

“Just because that's the rule doesn't mean that it's a proper rule,” Robertson said to anchors John Berman and Brianna Keilar on New Day. “And the reason why it's not a proper rule is that at that level, there would be zero pharmacology in a horse – zero – and it would have had no effect on this race. And one thing that you haven't heard, and you will not ever hear, is an equine pharmacologist to come out and say that 21 picograms, 25 picograms would have any pharmacology in a horse. They're not going to say that, because they can't say that.”

But the research – what little peer-reviewed research exists on betamethasone in horses — doesn't support that.

It's difficult to know what concentration of a drug in a horse does or doesn't influence a race; that's a separate question altogether, but there have been two peer-reviewed studies published in recent years which suggest that even small amounts of betamethasone in the blood may indeed reflect some effect on a horse's body.

A study published in the Journal of Veterinary Pharmacology and Therapeutics in 2015 sought to learn more about the pharmacology of intra-articular betamethasone injections in horses. Researchers administered two intra-articular betamethasone to eight 4-year-old Thoroughbreds and exercised them, then took blood and urine samples to check on levels of betamethasone and hydrocortisone for six weeks.

They found that the administration of betamethasone coincided with a reduced production by the horses' bodies of hydrocortisone. Hydrocortisone is naturally produced by the horse's body and acts similarly to its fellow corticosteroid betamethasone. There are synthetic versions of hydrocortisone out there in therapeutic medications, too.

It's thought that circulating levels of a closely-related, administered drug are read by the horse's brain similarly to the endogenously-produced substance, and the brain will halt production of its own corticosteroid until the synthetic corticosteroid wanes. The study found that the suppression of hydrocortisone was present for 96 to 120 hours after the administration of betamethasone.

The study found the last detectable level of betamethasone in plasma at an average of 64 hours post-injection and 69 hours in urine, although those measurements were using .05 nanograms per milliliter (or 50 picograms per mL) of plasma and .25 nanograms per milliliter (or 250 picograms per mL) of urine as their limit of detection – much larger concentrations than what was detected in the Medina Spirit case.

More interestingly though, in 2017 the journal Drug Testing and Analysis published a study which examined the concentrations of betamethasone in blood, urine, and joint fluid in Thoroughbreds. That study found that when betamethasone was injected in a horse's joint, concentrations of the drug in fell below detectable levels much sooner in plasma (96 hours) and urine (seven days) than it did in joint fluid. It took between 14 and 21 days for the drug to disappear from joint fluid in the joint that received the treatment.

“One of the basic tenants of pharmacokinetic/pharmacodynamic analysis is that blood levels reflect drug concentrations at the site of pharmacologic effect, thereby allowing the extent and duration of effect to be estimated based on blood concentrations,” wrote the study authors, led by Dr. Heather Kynch. “However, this does not appear to be the case for intra-articular corticosteroids.”

The study's findings were not wholly surprising, given that corticosteroids generally are known to be a little fickle in their withdrawal times. One previous study found triamcinolone in joint fluid for 35 days after a joint injection, and another found methylprednisolone 77 days after a single intra-articular dose.

Knych's study also noted that the diffusion of drugs from joints may vary from one joint to another.

“Although more comprehensive pharmacodynamic studies are necessary, these findings suggest that the anti-inflammatory effects may continue even though drug is no longer detected in blood,” wrote the Knych team. “A major concern with this finding is that horses may be able to return to racing before they are completely healed following an injury. Even though blood concentrations would be below the recommended threshold, allowing the horse to race, therapeutic drug concentrations in the joint may mask the clinical signs of an injury that is not completely healed. This could ultimately increase the risk of additional damage to the joint.”

At the time Knych and her team performed that study, the Racing Medication and Testing Consortium (RMTC) recommended a seven-day withdrawal of corticosteroids to clear a regulatory threshold of 10 picograms per mL. In the intervening years, jurisdictions like California and Kentucky backed up their corticosteroid administration timeframes to coincide with additional layers of pre-race veterinary checks performed to improve safety after the Santa Anita fatalities. In Kentucky, any level of corticosteroids like betamethasone in a post-race sample is a violation, based on the belief that the drug now can't be found farther out than 14 days post-administration.

Perhaps incredibly, those two studies seem to be the bulk of the peer-reviewed, published research that has been done on the behavior of betamethasone in a horse's body. It's not uncommon for research into equine medications to be limited, even for commonly-used therapeutic drugs like betamethasone.

Baffert's view on the Medina Spirit case would likely dismiss both studies as irrelevant. He asserts he gave the drug via a topical cream to treat a skin condition, not a joint injection, as was done in both studies. Further testing of the blood and urine from Medina Spirit will seek to clarify whether the betamethasone found in the horse came from an injection or an ointment, and it seems that will be an ongoing point of debate for his legal team. But with the limited peer-reviewed research available, the suggestion that the drug doesn't have any pharmacological effect at low levels of detection in blood is going to be an uphill battle.

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