Update on Medication Issues

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Update on Medication Issues

• Scot Waterman, DVM
• Executive Director
• Racing Medication Testing Consortium

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1. Penalties and the Model Rules
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Penalties and the Model Rules

• Old version
• Contained in RCI Uniform Drug Classification
  document
• Penalties based on RCI Class of the drug
• Penalties had large ranges for number of
  suspension days and fines
• No guidance on how to treat multiple violations
  or other circumstantial evidence

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Penalties and the Model Rules

• Reasons for change
• Classifications based entirely on pharmacology of
  drug but the question really needs to be whether
  the drug is appropriate to see in a racehorse
• Penalties should increase with repeat violations
• Other licensees should participate in the penalty
  phase especially repeat violators
• We need to define possible mitigating and
  aggravating circumstances

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Penalties and the Model Rules

• Flunixin (Banamine)
• RCI Class 4
• NSAID
• FDA-approved for the horse
• Many studies in the scientific literature in the
  horse
• Regulated by rule

• Meloxicam
• RCI Class 4
• NSAID
• Not FDA-approved for the horse
• No studies in the horse
• Not regulated by rule
• So, the question is why would someone use
  Meloxicam instead of Flunixin?

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Penalties and the Model Rules

• New version
• Took all drugs in RCI Classifications and
  assigned them into A, B, C or D groups
• Each drug was slotted based on criteria
• FDA approval1st for horse, 2nd for any reason?
• Legitimate therapeutic application?
• Identified as necessary by RMTC Vet Committee?
• Does an alternative exist?
• What is the current RCI Classification?

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Penalties and the Model Rules

• Diclofenac (Surpass)
• FDA-approved? Yes, for the horse
• Legitimate therapeutic application? Yes, as a
  topical anti-inflammatory
• Identified as necessary? Yes
• Does an alternative exist? No
• Current RCI Class? 4
• Penalty Class C
• 500 fine, loss of purse

• Meloxicam
• FDA-approved? No for horse, yes for dog, human
• Legitimate therapeutic application? No, no
  support in literature
• Identified as necessary? No
• Does an alternative exist? Yesflunixin, bute,
  ketoprofen
• Current RCI Class? 4
• Penalty Class B
• 15 day suspension, 500 fine, loss of purse

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Penalties and the Model Rules

• Other new tweaks
• Penalties for owner and horse potentially
• Ability to penalize veterinarian to same extent
  as trainer if culpability can be proven
• Licensed owners to be notified of any hearings as
  a result of a violation whether penalized or not
• Flexibility to let the penalty fit the
  circumstances of the casenot uniform penalties
  but a uniform approach to penalties

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Penalties and the Model Rules

• Mitigating and Aggravating Circumstances
• Each medication violation will have a unique set
  of circumstances even if the drug in question is
  the same
• This is true of any violationall murder
  defendants do not wind up with the same jail time
• Given the increased public scrutiny of the sport,
  violations need to be investigated and resulting
  penalties need to be well reasoned
• Alan Foreman will cover in detail tomorrow but
  lets spend some time on the concentration of the
  drug

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Penalties and the Model Rules

• How to interpret drug concentrations
• For the most part, you cant!
• There are too many unknowns
• Dose of drug
• Route of administration
• Frequency of administration
• Formulation of the drug
• Metabolic rate of the horse
• What you want is enough information to be able to
  make some educated guesses

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Penalties and the Model Rules

• Example
• You are given a positive lab report of
  acepromazine with a concentration of 25
  nanograms/ml in urine
• Possibilities
• Trainer was giving 25 mg once a day orally
  because horse is hard to handle
• Horse shipped in three days ago and was given an
  injection to help with van ride
• Horse is a basket case in the paddock so a small
  amount was given IV with furosemide to take the
  edge off
• All three are legitimate scenarios for that
  concentration of drughow do you try to
  differentiate and do you need to?

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Penalties and the Model Rules

• What kind information can help you
• Pharmacokinetics (the study of elimination of a
  drug over time)
• Elimination curves can be produced that give you
  concentration vs. time
• Plasma correlates much better than urine
  generally
• Difficulties
• Not every drug has been studied
• Small number of horses often used
• Furosemide complicates for urine
• Some drugs not detectable in plasma for a long
  enough period of time

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Pharmacokinetic Analysis
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Penalties and the Model Rules

• What kind information can help you
• Veterinary Records
• They can be changed/created/edited to fit the
  story but still useful
• Interviews
• Get the Vet Records first, look for consistency
• If positive has been reported in urine, plasma
  may be useful to look at

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Penalties and the Model Rules

• 25 ng/ml acepromazine in urine
• PK chart25 mg IV single dose

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Penalties and the Model Rules

• 25 ng/ml acepromazine in urine
• Lab tests the plasmano detectable concentration
  of aceproamzine
• Records show horse shipped in two days ago
• Trainer has one bute overage 10 years ago
• Not 100 but circumstances seem to fit with a
  single injection for tranquilization prior to
  shipping
• Would fit with the minimum or could even mitigate
  down to below the minimum since there was likely
  no intent to cheat

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RMTC Administration Studies

• Have 20-horse data for
• Butorphanol
• Methocarbamol (Robaxin)
• Pyrilamine
• Clenbuterol
• Firocoxib (Equioxx)
• Glycopyrrolate
• Administrations complete for
• Lidocaine, Mepivacaine, Acepromazine, Detomidine
• Administrations planned for
• Dantrolene, Hydroxyzine, Fluphenazine, Xylazine,
  Albuterol

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2. Therapeutic medicationscurrent events
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Furosemide (Salix, Lasix)

• 90 of horses suffer from some degree of EIPH,
  estimated that industry cost of EIPH approaches
  100 million dollars
• Working theory is that increase in circulating
  RBCs during exercise increases blood pressure in
  blood vessels of lung
• Furosemide thought to lower blood pressure in
  lungs by reducing fluid component of blood
• Published science very unclear on whether this is
  the case

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Furosemide (Salix, Lasix)

• Lasix Perceptions
• We are breeding generations of bleeders
• Lasix masks the presence of other drugs
• Lasix is somehow linked to soundness issues

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Furosemide (Salix, Lasix)

• SAFE Study
• Double-blinded study using horses that have never
  received furosemide before in actual race
  conditions for purse money in South Africa
• Horses receiving saline instead of furosemide had
  increased severity of EIPH
• 67.5 of horses that bled when receiving saline
  had improved EIPH severity scores by at least one
• ConclusionEIPH incidence and severity was
  improved by pre-race administration of furosemide

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NSAIDS

• One of three (phenylbutazone, flunixin,
  ketoprofen) can be administered 24 hours out
• Must be administered with a single IV injection
• Threshold concentration used to enforce
• 20 ng/ml for flunixin
• 10 ng/ml for ketoprofen
• 5 mcg/ml for phenylbutazone
• Studies indicate analgesic effect is gone by 12
  hours after IV injection

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NSAIDS

• Regulatory veterinarians feel the 24-hour
  administration impacts their ability to perform
  pre-race exams
• Some science seems to support, some does not
• Collecting samples in some states at the time of
  the pre-race exam to get an idea of plasma
  concentrations
• On the table- pushing administration out to 48
  hours (similar to Canada) or reducing
  phenylbutazone threshold to 2 mcg/ml
• Will have an answer hopefully by end of year

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Anabolic Steroids

• Model rule has been in place now for 6-18 months
  depending on jurisdiction
• Rule has basically eliminated the use of the
  usual anabolic steroids
• Chemists reporting no detectable anabolic agents
  in post-race samples
• Revised rule with plasma thresholds proposed to
  RCI
• Labs with proper instrumentation will likely
  switch to plasma testing

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Anabolic Steroids Issues

• The program gelding with high testosterone
• Recommend a HCG Challenge Test to determine
  whether residual testicular tissue is present
• If positive horse is classified for regulatory
  purposes as a rig and kept as a gelding for
  program
• Rig notation is sent to lab with subsequent
  samples which are excused from testosterone
  testing
• Hermaphrodites
• One Standardbred mare on east coast throws
  fillies with internal male sex organs

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Anabolic steroids

• Starting to see replacement substances begin to
  be a problem
• High-dose clenbuterol
• Ractopamine
• Ethylestrenol

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Coming Attractions

• Corticosteroids
• RCI Class 4 Substances
• Anti-inflammatory in action
• Very diverse group of drugs, wide number of uses
• Some are difficult to test for and process is
  complicated by multiple routes of administration
• Many states choose to use testing budget
  elsewhere, mostly due to Class 4 status
• Abuse, particularly intra-articular, is
  significant anecdotally especially in claiming
  horses

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Coming Attractions

• Corticosteroids
• Pennsylvania has adopted a 7-day ban on
  intra-articular injections
• Questionable whether this can be enforced
  currently
• RMTC is funding studies on the corticosteroids
  which will look to generate PK data
• Also looking at dynamic markers

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3. RMTC Drug Testing Initiatives
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RMTCDrug Testing Initiatives

• Post-race testing in the United States
• Currently 18 laboratories conducting testing
• Only 5 labs ISO 17025 accredited
• 30 of samples were tested by an accredited lab
  in 08
• Funding is dramatically different state-to-state
• No industry standards for US testing labs
• Animal selection strategies havent changed in
  years

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RMTCDrug Testing Initiatives

• Committee formed in September 2008
• First meeting- design the best system for US Drug
  Testing irrespective of funding and political
  concerns
• Consensus that we should utilize laboratory
  standards developed by the World Anti-Doping
  Association where applicable and work toward the
  development of a performance-based system
• Other related topics discussed- next generation
  of lab directors, samples selection, frozen
  samples, harmonization nationally and
  internationally

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RMTCDrug Testing Initiatives

• Creation of Industry Standards for Labs
• Edited version of the Lab Standards document
  created by the World Anti-Doping Association has
  been developed by the committee
• Standards rely on ISO 17025 accreditation as the
  first step
• An external proficiency program is then conducted
• Labs failing proficiency cannot conduct testing
• A percentage of the laboratory budget is mandated
  to be directed toward research
• Current QAP programs (TIP IDTA) salvaged for
  2009 via financial arrangement between RCI and
  RMTC

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RMTCDrug Testing Initiatives

• Creation of Industry Standards for Labs
  (continued)
• Result will create the first set of industry
  standards for post-race testing labs in US
• States/industry will have a document to sell in
  order to provide incremental funding for lab to
  meet standards
• Will need funding for the industry organization
  that takes on the role of WADA
• Standards would be a perfect fit for the idea of
  a national compact

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RMTCDrug Testing Initiatives

• Post-doctoral and graduate student recruitment
• Our Laboratory Directors are agingwho replaces
  them?
• Those with research programs that are racing
  related could do more with capable students
• Developing a comprehensive program to target
  individuals with pharmacology/veterinary/chemistry
  backgrounds to place in research positions and
  will also utilize racing laboratories and
  possibly U of A RTIP for broad racing education
• Initial cost 150,000-300,000

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RMTCDrug Testing Initiatives

• Sample Collection
• Is testing winners the most efficient use of
  testing dollars?
• McKinsey Report suggested using a matrix based on
  odds and finish place of the horse
• Possibility of collection without testing
• Frozen Sample Program
• Possible deterrent effect and useful for
  intelligence information
• Program is funded for 2009 and RMTC will
  administer

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RMTCDrug Testing Initiatives

• Pleased with progress in a short period
• Will need broad industry support to implement
• Incremental funding will be needed
• Industry needs to support commissions at
  legislative level
• Will need industry organizations with sticks to
  use them