Update on Medication Issues Scot Waterman, DVM Executive Director Racing Medication & Testing Consortium

Update on Update on Medication Medication IssuesIssues

Scot Waterman, DVMScot Waterman, DVMExecutive DirectorExecutive Director

Racing Medication & Testing Racing Medication & Testing ConsortiumConsortium

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

Penalties and the Penalties and the Model RulesModel Rules Old version:Old version:

– Contained in RCI Uniform Drug Contained in RCI Uniform Drug Classification documentClassification document

– Penalties based on RCI Class of the Penalties based on RCI Class of the drugdrug

– Penalties had large ranges for Penalties had large ranges for number of suspension days and finesnumber of suspension days and fines

– No guidance on how to treat multiple No guidance on how to treat multiple violations or other circumstantial violations or other circumstantial evidenceevidence

Penalties and the Penalties and the Model RulesModel Rules

Reasons for change:Reasons for change:– Classifications based entirely on Classifications based entirely on

pharmacology of drug but the question pharmacology of drug but the question really needs to be whether the drug is really needs to be whether the drug is appropriate to see in a racehorseappropriate to see in a racehorse

– Penalties should increase with repeat Penalties should increase with repeat violationsviolations

– Other licensees should participate in Other licensees should participate in the penalty phase especially repeat the penalty phase especially repeat violatorsviolators

– We need to define possible mitigating We need to define possible mitigating and aggravating circumstancesand aggravating circumstances


Flunixin Flunixin (Banamine)(Banamine)– RCI Class 4RCI Class 4– NSAIDNSAID– FDA-approved FDA-approved

for the horsefor the horse– Many studies in Many studies in

the scientific the scientific literature in the literature in the horsehorse

– Regulated by Regulated by rulerule

MeloxicamMeloxicam– RCI Class 4RCI Class 4– NSAIDNSAID– Not FDA-approved Not FDA-approved

for the horsefor the horse– No studies in the No studies in the

horsehorse– Not regulated by Not regulated by

rulerule– So, the question is So, the question is

why would why would someone use someone use Meloxicam instead Meloxicam instead of Flunixin?of Flunixin?


New version:New version:– Took all drugs in RCI Classifications and Took all drugs in RCI Classifications and

assigned them into A, B, C or D groupsassigned them into A, B, C or D groups– Each drug was slotted based on criteria:Each drug was slotted based on criteria:

1.1. FDA approval…1FDA approval…1stst for horse, 2 for horse, 2ndnd for any for any reason?reason?

2.2. Legitimate therapeutic application?Legitimate therapeutic application?3.3. Identified as necessary by RMTC Vet Identified as necessary by RMTC Vet

Committee?Committee?4.4. Does an alternative exist?Does an alternative exist?5.5. What is the current RCI Classification?What is the current RCI Classification?

Penalties and the Penalties and the Model RulesModel Rules Diclofenac Diclofenac

(Surpass)(Surpass)1.1. FDA-approved? Yes, for FDA-approved? Yes, for

the horsethe horse2.2. Legitimate therapeutic Legitimate therapeutic

application? Yes, as a application? Yes, as a topical anti-topical anti-inflammatoryinflammatory

3.3. Identified as Identified as necessary? Yesnecessary? Yes

4.4. Does an alternative Does an alternative exist? Noexist? No

5.5. Current RCI Class? 4Current RCI Class? 4

– Penalty Class “C”Penalty Class “C”– $500 fine, loss of purse$500 fine, loss of purse

MeloxicamMeloxicam1.1. FDA-approved? No for FDA-approved? No for

horse, yes for dog, horse, yes for dog, humanhuman

2.2. Legitimate therapeutic Legitimate therapeutic application? No, no application? No, no support in literaturesupport in literature

3.3. Identified as Identified as necessary? Nonecessary? No

4.4. Does an alternative Does an alternative exist? Yes…flunixin, exist? Yes…flunixin, bute, ketoprofenbute, ketoprofen

5.5. Current RCI Class? 4Current RCI Class? 4

– Penalty Class “B”Penalty Class “B”– 15 day suspension, 15 day suspension,

$500 fine, loss of purse$500 fine, loss of purse


Other new tweaks:Other new tweaks:– Penalties for owner and horse potentiallyPenalties for owner and horse potentially– Ability to penalize veterinarian to same Ability to penalize veterinarian to same

extent as trainer if culpability can be provenextent as trainer if culpability can be proven– Licensed owners to be notified of any Licensed owners to be notified of any

hearings as a result of a violation whether hearings as a result of a violation whether penalized or notpenalized or not

– Flexibility to let the penalty fit the Flexibility to let the penalty fit the circumstances of the case…not circumstances of the case…not uniform uniform penaltiespenalties but a but a uniform approach to uniform approach to penaltiespenalties


Mitigating and Aggravating Mitigating and Aggravating Circumstances:Circumstances:– Each medication violation will have a unique set Each medication violation will have a unique set

of circumstances even if the drug in question is of circumstances even if the drug in question is the samethe same

– This is true of any violation…all murder This is true of any violation…all murder defendants do not wind up with the same jail timedefendants do not wind up with the same jail time

– Given the increased public scrutiny of the sport, Given the increased public scrutiny of the sport, violations need to be investigated and resulting violations need to be investigated and resulting penalties need to be well reasonedpenalties need to be well reasoned

– Alan Foreman will cover in detail tomorrow but Alan Foreman will cover in detail tomorrow but let’s spend some time on the concentration of the let’s spend some time on the concentration of the drugdrug


How to interpret drug How to interpret drug concentrations:concentrations:– For the most part, you can’t!For the most part, you can’t!– There are too many unknowns:There are too many unknowns:

Dose of drugDose of drug Route of administrationRoute of administration Frequency of administrationFrequency of administration Formulation of the drugFormulation of the drug Metabolic rate of the horseMetabolic rate of the horse

– What you want is enough information to be What you want is enough information to be able to make some educated guessesable to make some educated guesses


Example:Example:– You are given a positive lab report of You are given a positive lab report of

acepromazine with a concentration of 25 acepromazine with a concentration of 25 nanograms/ml in urine nanograms/ml in urine

– Possibilities:Possibilities: Trainer was giving 25 mg once a day Trainer was giving 25 mg once a day

orally because horse is hard to handleorally because horse is hard to handle Horse shipped in three days ago and was Horse shipped in three days ago and was

given an injection to help with van ridegiven an injection to help with van ride Horse is a basket case in the paddock so a Horse is a basket case in the paddock so a

small amount was given IV with small amount was given IV with furosemide to take the edge offfurosemide to take the edge off

– All three are legitimate scenarios for All three are legitimate scenarios for that concentration of drug…how do you that concentration of drug…how do you try to differentiate and do you need to?try to differentiate and do you need to?


What kind information can help you:What kind information can help you:– Pharmacokinetics (the study of Pharmacokinetics (the study of

elimination of a drug over time) elimination of a drug over time) Elimination curves can be produced that give Elimination curves can be produced that give

you concentration vs. timeyou concentration vs. time Plasma correlates much better than urine Plasma correlates much better than urine

generallygenerally– DifficultiesDifficulties

Not every drug has been studiedNot every drug has been studied Small number of horses often usedSmall number of horses often used Furosemide complicates for urineFurosemide complicates for urine Some drugs not detectable in plasma for a Some drugs not detectable in plasma for a

long enough period of timelong enough period of time

Pharmacokinetic Pharmacokinetic AnalysisAnalysis

0 200 400 600 80010

100

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Time, minutes

Pla

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carb

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g/m

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RMTC Testosterone StudyUF Results

0 10 20 301

10

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Time (days)

Pla

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pg

/mL


What kind information can help What kind information can help you:you:– Veterinary Records Veterinary Records

They can be changed/created/edited to fit They can be changed/created/edited to fit the story but still usefulthe story but still useful

– InterviewsInterviews Get the Vet Records first, look for Get the Vet Records first, look for

consistency consistency

– If positive has been reported in urine, If positive has been reported in urine, plasma may be useful to look atplasma may be useful to look at

Penalties and the Penalties and the Model RulesModel Rules 25 ng/ml acepromazine in urine:25 ng/ml acepromazine in urine:

– PK chart…25 mg IV single dosePK chart…25 mg IV single dose


25 ng/ml acepromazine in urine:25 ng/ml acepromazine in urine:– Lab tests the plasma…no detectable Lab tests the plasma…no detectable

concentration of aceproamzineconcentration of aceproamzine– Records show horse shipped in two days Records show horse shipped in two days

agoago– Trainer has one bute overage 10 years agoTrainer has one bute overage 10 years ago

Not 100% but circumstances seem to Not 100% but circumstances seem to fit with a single injection for fit with a single injection for tranquilization prior to shippingtranquilization prior to shipping

Would fit with the minimum or could Would fit with the minimum or could even mitigate down to below the even mitigate down to below the minimum since there was likely no minimum since there was likely no intent to cheatintent to cheat

RMTC Administration RMTC Administration StudiesStudies Have 20-horse data for:Have 20-horse data for:

– ButorphanolButorphanol– Methocarbamol (Robaxin®)Methocarbamol (Robaxin®)– PyrilaminePyrilamine– ClenbuterolClenbuterol– Firocoxib (Equioxx®)Firocoxib (Equioxx®)– GlycopyrrolateGlycopyrrolate

Administrations complete for:Administrations complete for:– Lidocaine, Mepivacaine, Acepromazine, Lidocaine, Mepivacaine, Acepromazine,

DetomidineDetomidine Administrations planned for:Administrations planned for:

– Dantrolene, Hydroxyzine, Fluphenazine, Dantrolene, Hydroxyzine, Fluphenazine, Xylazine, AlbuterolXylazine, Albuterol

2.2. Therapeutic Therapeutic medications—current medications—current eventsevents

Furosemide (Salix, Furosemide (Salix, Lasix)Lasix) 90+% of horses suffer from some 90+% of horses suffer from some

degree of EIPH, estimated that degree of EIPH, estimated that industry cost of EIPH approaches $100 industry cost of EIPH approaches $100 million dollarsmillion dollars

Working theory is that increase in Working theory is that increase in circulating RBCs during exercise circulating RBCs during exercise increases blood pressure in blood increases blood pressure in blood vessels of lungvessels of lung

Furosemide thought to lower blood Furosemide thought to lower blood pressure in lungs by reducing fluid pressure in lungs by reducing fluid component of bloodcomponent of blood

Published science very unclear on Published science very unclear on whether this is the casewhether this is the case

Furosemide (Salix, Furosemide (Salix, Lasix)Lasix)

Lasix Lasix PerceptionsPerceptions– We are breeding We are breeding

generations of generations of bleedersbleeders

– Lasix masks the Lasix masks the presence of presence of other drugsother drugs

– Lasix is somehow Lasix is somehow linked to linked to soundness issuessoundness issues

Furosemide (Salix, Furosemide (Salix, Lasix)Lasix) SAFE Study:SAFE Study:

– Double-blinded study using horses that have Double-blinded study using horses that have never received furosemide before in actual race never received furosemide before in actual race conditions for purse money in South Africaconditions for purse money in South Africa

– Horses receiving saline instead of furosemide Horses receiving saline instead of furosemide had increased severity of EIPHhad increased severity of EIPH

– 67.5% of horses that bled when receiving saline 67.5% of horses that bled when receiving saline had improved EIPH severity scores by at least had improved EIPH severity scores by at least oneone

– Conclusion…EIPH incidence and severity was Conclusion…EIPH incidence and severity was improved by pre-race administration of improved by pre-race administration of furosemidefurosemide

NSAIDSNSAIDS

One of three (phenylbutazone, flunixin, One of three (phenylbutazone, flunixin, ketoprofen) can be administered 24 ketoprofen) can be administered 24 hours outhours out

Must be administered with a single IV Must be administered with a single IV injectioninjection

Threshold concentration used to Threshold concentration used to enforceenforce– 20 ng/ml for flunixin20 ng/ml for flunixin– 10 ng/ml for ketoprofen10 ng/ml for ketoprofen– 5 mcg/ml for phenylbutazone5 mcg/ml for phenylbutazone

Studies indicate analgesic effect is Studies indicate analgesic effect is gone by 12 hours after IV injection gone by 12 hours after IV injection

NSAIDSNSAIDS

Regulatory veterinarians feel the 24-Regulatory veterinarians feel the 24-hour administration impacts their hour administration impacts their ability to perform pre-race examsability to perform pre-race exams

Some science seems to support, some Some science seems to support, some does notdoes not

Collecting samples in some states at Collecting samples in some states at the time of the pre-race exam to get the time of the pre-race exam to get an idea of plasma concentrationsan idea of plasma concentrations

On the table- pushing administration On the table- pushing administration out to 48 hours (similar to Canada) out to 48 hours (similar to Canada) or reducing phenylbutazone or reducing phenylbutazone threshold to 2 mcg/mlthreshold to 2 mcg/ml

Will have an answer hopefully by end Will have an answer hopefully by end of yearof year

Anabolic SteroidsAnabolic Steroids

Model rule has been in place now for Model rule has been in place now for 6-18 months depending on 6-18 months depending on jurisdictionjurisdiction

Rule has basically eliminated the Rule has basically eliminated the use of the usual anabolic steroidsuse of the usual anabolic steroids

Chemists reporting no detectable Chemists reporting no detectable anabolic agents in post-race samplesanabolic agents in post-race samples

Revised rule with plasma thresholds Revised rule with plasma thresholds proposed to RCIproposed to RCI

Labs with proper instrumentation Labs with proper instrumentation will likely switch to plasma testingwill likely switch to plasma testing

Anabolic Steroids Anabolic Steroids IssuesIssues The program gelding with high The program gelding with high

testosteronetestosterone– Recommend a HCG Challenge Test to Recommend a HCG Challenge Test to

determine whether residual testicular determine whether residual testicular tissue is presenttissue is present

– If “positive” horse is classified for If “positive” horse is classified for regulatory purposes as a “rig” and kept as a regulatory purposes as a “rig” and kept as a gelding for programgelding for program

– ““Rig” notation is sent to lab with Rig” notation is sent to lab with subsequent samples which are excused subsequent samples which are excused from testosterone testingfrom testosterone testing

HermaphroditesHermaphrodites– One Standardbred mare on east coast One Standardbred mare on east coast

throws fillies with internal male sex organsthrows fillies with internal male sex organs

Anabolic steroids Anabolic steroids

Starting to see Starting to see “replacement” “replacement” substances substances begin to be a begin to be a problem:problem:– High-dose High-dose

clenbuterolclenbuterol– RactopamineRactopamine– EthylestrenolEthylestrenol

Coming AttractionsComing Attractions

CorticosteroidsCorticosteroids– RCI Class 4 SubstancesRCI Class 4 Substances– Anti-inflammatory in actionAnti-inflammatory in action– Very diverse group of drugs, wide number Very diverse group of drugs, wide number

of usesof uses– Some are difficult to test for and process Some are difficult to test for and process

is complicated by multiple routes of is complicated by multiple routes of administrationadministration

– Many states choose to use testing budget Many states choose to use testing budget elsewhere, mostly due to Class 4 statuselsewhere, mostly due to Class 4 status

– Abuse, particularly intra-articular, is Abuse, particularly intra-articular, is significant anecdotally especially in significant anecdotally especially in claiming horsesclaiming horses

Coming AttractionsComing Attractions

CorticosteroidsCorticosteroids– Pennsylvania has adopted a 7-day Pennsylvania has adopted a 7-day

ban on intra-articular injectionsban on intra-articular injections– Questionable whether this can be Questionable whether this can be

enforced currentlyenforced currently– RMTC is funding studies on the RMTC is funding studies on the

corticosteroids which will look to corticosteroids which will look to generate PK datagenerate PK data

– Also looking at dynamic markersAlso looking at dynamic markers

3.3. RMTC Drug RMTC Drug Testing InitiativesTesting Initiatives

RMTCRMTCDrug Testing Drug Testing InitiativesInitiatives Post-race testing in the United Post-race testing in the United

States:States:– Currently 18 laboratories conducting Currently 18 laboratories conducting

testingtesting– Only 5 labs ISO 17025 accreditedOnly 5 labs ISO 17025 accredited

30% of samples were tested by an 30% of samples were tested by an accredited lab in ‘08accredited lab in ‘08

– Funding is dramatically different state-Funding is dramatically different state-to-stateto-state

– No industry standards for US testing labsNo industry standards for US testing labs– Animal selection strategies haven’t Animal selection strategies haven’t

changed in yearschanged in years

RMTCRMTCDrug Testing Drug Testing InitiativesInitiatives Committee formed in September 2008Committee formed in September 2008 First meeting- design the best system for First meeting- design the best system for

US Drug Testing irrespective of funding and US Drug Testing irrespective of funding and political concernspolitical concerns

Consensus that we should utilize laboratory Consensus that we should utilize laboratory standards developed by the World Anti-standards developed by the World Anti-Doping Association where applicable and Doping Association where applicable and work toward the development of a work toward the development of a performance-based systemperformance-based system

Other related topics discussed- next Other related topics discussed- next generation of lab directors, samples generation of lab directors, samples selection, frozen samples, harmonization selection, frozen samples, harmonization nationally and internationallynationally and internationally

RMTCRMTCDrug Testing Drug Testing InitiativesInitiatives1.1. Creation of Industry Standards for Creation of Industry Standards for

Labs:Labs:– Edited version of the Lab Standards Edited version of the Lab Standards

document created by the World Anti-document created by the World Anti-Doping Association has been developed by Doping Association has been developed by the committeethe committee

Standards rely on ISO 17025 accreditation Standards rely on ISO 17025 accreditation as the first step as the first step

An external proficiency program is then An external proficiency program is then conductedconducted

Labs failing proficiency cannot conduct Labs failing proficiency cannot conduct testingtesting

– A percentage of the laboratory budget is A percentage of the laboratory budget is mandated to be directed toward researchmandated to be directed toward research

– Current QAP programs (TIP & IDTA) Current QAP programs (TIP & IDTA) salvaged for 2009 via financial salvaged for 2009 via financial arrangement between RCI and RMTCarrangement between RCI and RMTC

RMTCRMTCDrug Testing Drug Testing InitiativesInitiatives1.1. Creation of Industry Standards Creation of Industry Standards

for Labs (continued):for Labs (continued):– Result will create the first set of Result will create the first set of

industry standards for post-race industry standards for post-race testing labs in UStesting labs in US

– States/industry will have a document to States/industry will have a document to “sell” in order to provide incremental “sell” in order to provide incremental funding for lab to meet standards funding for lab to meet standards

– Will need funding for the industry Will need funding for the industry organization that takes on the role of organization that takes on the role of WADA WADA

– Standards would be a perfect fit for the Standards would be a perfect fit for the idea of a national compactidea of a national compact

RMTCRMTCDrug Testing Drug Testing InitiativesInitiatives2.2. Post-doctoral and graduate student Post-doctoral and graduate student

recruitment:recruitment:– Our Laboratory Directors are aging…who Our Laboratory Directors are aging…who

replaces them?replaces them?– Those with research programs that are racing Those with research programs that are racing

related could do more with capable studentsrelated could do more with capable students– Developing a comprehensive program to Developing a comprehensive program to

target individuals with target individuals with pharmacology/veterinary/chemistry pharmacology/veterinary/chemistry backgrounds to place in research positions backgrounds to place in research positions and will also utilize racing laboratories and and will also utilize racing laboratories and possibly U of A RTIP for broad racing possibly U of A RTIP for broad racing educationeducation

– Initial cost $150,000-300,000Initial cost $150,000-300,000

RMTCRMTCDrug Testing Drug Testing InitiativesInitiatives3.3. Sample CollectionSample Collection

– Is testing winners the most efficient Is testing winners the most efficient use of testing dollars?use of testing dollars?

– McKinsey Report suggested using a McKinsey Report suggested using a matrix based on odds and finish place matrix based on odds and finish place of the horseof the horse

– Possibility of collection without testingPossibility of collection without testing

4.4. Frozen Sample ProgramFrozen Sample Program– Possible deterrent effect and useful for Possible deterrent effect and useful for

intelligence informationintelligence information– Program is funded for 2009 and RMTC Program is funded for 2009 and RMTC

will administerwill administer

RMTCRMTCDrug Testing Drug Testing InitiativesInitiatives Pleased with progress in a short Pleased with progress in a short

periodperiod Will need broad industry support Will need broad industry support

to implementto implement– Incremental funding will be neededIncremental funding will be needed– Industry needs to support Industry needs to support

commissions at legislative levelcommissions at legislative level Will need industry organizations Will need industry organizations

with sticks to use themwith sticks to use them

Documents

Update on Medication Issues Scot Waterman, DVM Executive Director Racing Medication & Testing Consortium