Drug Control in Drug Control in Horse Racing in the Horse Racing in the U.S.U.S.Scot Waterman, DVMScot Waterman, DVMExecutive DirectorExecutive Director

Racing Medication & Testing Racing Medication & Testing ConsortiumConsortium

U.S. Regulatory U.S. Regulatory FrameworkFramework

U.S. Regulatory U.S. Regulatory FrameworkFramework

State statute enables a state agency State statute enables a state agency to govern pari-mutuel wageringto govern pari-mutuel wagering

Commission has power to write, Commission has power to write, enforce and adjudicate rules…enforce and adjudicate rules…executive, quasi-judicial, quasi-executive, quasi-judicial, quasi-legislativelegislative

Commissioners are usually Commissioners are usually appointed by the governorappointed by the governor

No US federal government No US federal government counterpart to the CPMAcounterpart to the CPMA

U.S. Regulatory U.S. Regulatory FrameworkFramework

Makeup of commission varies state-by-stateMakeup of commission varies state-by-state– Some states do not allow those involved in the Some states do not allow those involved in the

industry day-to-day to serve as commissionersindustry day-to-day to serve as commissioners– Number of commissioners (as low as 1, as high as Number of commissioners (as low as 1, as high as

13)13) Funding for operations varies state-by-stateFunding for operations varies state-by-state

– Majority of states funded through general funds Majority of states funded through general funds but some based on revenue sources from handlebut some based on revenue sources from handle

Rulemaking process varies state-by-stateRulemaking process varies state-by-state– NJ, NY, CA from start to finish process can take NJ, NY, CA from start to finish process can take

over one year. Some states also have regulations over one year. Some states also have regulations encoded in statute…need to involve legislature to encoded in statute…need to involve legislature to changechange

U.S. Regulatory U.S. Regulatory Framework—Framework—ChallengesChallenges Commission only quasi-legislativeCommission only quasi-legislative

– Generally some state legislature oversight Generally some state legislature oversight which creates another potential hurdle for which creates another potential hurdle for model rulesmodel rules

Commission only quasi-judicialCommission only quasi-judicial– Violations appealed to state court which Violations appealed to state court which

historically have reduced significant historically have reduced significant penaltiespenalties

Commission budgets always at riskCommission budgets always at risk Local politics more important than Local politics more important than

national politicsnational politics

Racing Medication & Racing Medication & Testing ConsortiumTesting Consortium

RMTC HistoryRMTC History

Formation:Formation:– Began with the AAEP Medication Began with the AAEP Medication

Summit, December 2001Summit, December 2001– Summit designed to determine level of Summit designed to determine level of

consensus on uniform medication consensus on uniform medication policypolicy

– All organization that participated in All organization that participated in original meeting are still involved nine original meeting are still involved nine years lateryears later

– Organization has moved beyond rule Organization has moved beyond rule uniformity as a singular goaluniformity as a singular goal

Incorporated as a 501 (c) (3) Incorporated as a 501 (c) (3) charitable organization since 2003charitable organization since 2003

RMTC BoardRMTC Board

HorsemenHorsemen—THA, HBPA, CTT—THA, HBPA, CTT TracksTracks-Magna, Churchill, Oak Tree, Del -Magna, Churchill, Oak Tree, Del

Mar, HTA, TRA, NYRA, KeenelandMar, HTA, TRA, NYRA, Keeneland Owners/BreedersOwners/Breeders—TOBA, TOC, KTA—TOBA, TOC, KTA VeterinariansVeterinarians—AAEP —AAEP SecuritySecurity—TRPB —TRPB Regulatory AssociationRegulatory Association—RCI—RCI Breed Registries/OtherBreed Registries/Other—AQHA, The —AQHA, The

Jockey Club, NTRA, USTA, Jockey Club, NTRA, USTA, Hambeltonian Society, Arabian Jockey Hambeltonian Society, Arabian Jockey ClubClub

JockeysJockeys—Jockey’s Guild—Jockey’s Guild

Goals and ObjectivesGoals and Objectives

Uniform medication rulesUniform medication rules Uniform testing procedures and Uniform testing procedures and

laboratory accreditationlaboratory accreditation Uniform thresholds and withdrawal Uniform thresholds and withdrawal

guidelines for therapeutic medicationsguidelines for therapeutic medications Unbiased source of information on Unbiased source of information on

medication issues for state racing medication issues for state racing commissions commissions

Develop intelligence on new threats to Develop intelligence on new threats to integrityintegrity

Better communication regarding Better communication regarding medication issuesmedication issues

RMTC Goals and RMTC Goals and ObjectivesObjectives Generally successful in the Generally successful in the

development of model medication development of model medication policies and encouragement of policies and encouragement of adoption at state leveladoption at state level– Large board viewed as an “industry Large board viewed as an “industry

consensus” once language is completedconsensus” once language is completed– Have been able to overcome some of the Have been able to overcome some of the

parochial issues as state levelparochial issues as state level– Able represent RMTC in person at state Able represent RMTC in person at state

commission meetings when requestedcommission meetings when requested– Development of a network of individuals Development of a network of individuals

within commissions to assist in the within commissions to assist in the adoption processadoption process

RMTC Goals and RMTC Goals and ObjectivesObjectives US closer to uniformity than ever US closer to uniformity than ever

beforebefore Challenges still remain:Challenges still remain:

– PenaltiesPenalties Difficult to get stewards/commissions to Difficult to get stewards/commissions to

depart from status quodepart from status quo

– How to make smaller states relevant, How to make smaller states relevant, part of processpart of process

– Commissions that want to look Commissions that want to look tougher than anyone elsetougher than anyone else

– Grinding process, impatient industryGrinding process, impatient industry

RMTC RMTC Pharmacokinetic Pharmacokinetic ProgramProgram

Uniform thresholds Uniform thresholds and withdrawal timesand withdrawal times

First step…create a priority list of First step…create a priority list of drugs for study:drugs for study:– AAEP was asked to put together a AAEP was asked to put together a

committee of veterinarians to identify committee of veterinarians to identify “most essential” therapeutic “most essential” therapeutic medicationsmedications

– List was then prioritized based on the List was then prioritized based on the number of positive tests caused in the number of positive tests caused in the USA over a five year period and survey USA over a five year period and survey results of practitionersresults of practitioners

Uniform thresholds Uniform thresholds and withdrawal timesand withdrawal times

Second step…fund administration Second step…fund administration studies on each drug at relevant studies on each drug at relevant dosesdoses– FDA formula used for drug residues in FDA formula used for drug residues in

milk used to calculate threshold at a milk used to calculate threshold at a given withdrawal periodgiven withdrawal period

– Minimum of twenty horses used for each Minimum of twenty horses used for each study to reduce the study to reduce the k k factor of the factor of the formulaformula

– Withdrawal time based on end of Withdrawal time based on end of pharmacologic activity when knownpharmacologic activity when known

Study DesignStudy Design

Test substance Test substance – Blood primaryBlood primary– Urine secondaryUrine secondary

Laboratory methodsLaboratory methods– LC-MS at lowest attainable limit of detection LC-MS at lowest attainable limit of detection

(LOD) using latest instrumentation and (LOD) using latest instrumentation and methodologymethodology

Drug Administrations Drug Administrations – Drugs were administered IV as single dose Drugs were administered IV as single dose

except for select drugsexcept for select drugs– Blood and urine samples were collected at Blood and urine samples were collected at

specific times after drug administration – specific times after drug administration – samples were sent to testing laboratories for samples were sent to testing laboratories for analysisanalysis

– ““Cheater doses” studied when intelligence on Cheater doses” studied when intelligence on dose/route/time is availabledose/route/time is available

University of Florida University of Florida Equine Performance Equine Performance LaboratoryLaboratory DirectorDirector

– Pat Colahan, DVMPat Colahan, DVM HorsesHorses

– BreedsBreeds ThoroughbredThoroughbred Standardbred (specific studies)Standardbred (specific studies)

– GenderGender Geldings and maresGeldings and mares

– AgeAge 3-10 years3-10 years

– FitnessFitness Trained on treadmill and fitness assessed Trained on treadmill and fitness assessed

periodicallyperiodically

Equine Performance Equine Performance LaboratoryLaboratory Training and Fitness AssessmentTraining and Fitness Assessment

– Exercised 3 times per week on high-speed Exercised 3 times per week on high-speed treadmilltreadmill

Trot for 0.6 km at 4.0 m/s, gallop for 2 km at Trot for 0.6 km at 4.0 m/s, gallop for 2 km at 8 m/s, and trot for 0.6 km at 4 m/s 8 m/s, and trot for 0.6 km at 4 m/s

Treadmill horizontal on Monday and inclined Treadmill horizontal on Monday and inclined 6 degrees on Wednesday and Friday6 degrees on Wednesday and Friday

– Incremental Exercise Test to ExhaustionIncremental Exercise Test to Exhaustion Warm up on the treadmill at 4 m/s for 5 min Warm up on the treadmill at 4 m/s for 5 min

before the start of the test; exercise for 1 min before the start of the test; exercise for 1 min each at 9, 10, 11, 12, 13 and 14 m/s until they each at 9, 10, 11, 12, 13 and 14 m/s until they are unable to maintain the speed.are unable to maintain the speed.

Blood samples collected for lactate and pHBlood samples collected for lactate and pH– Require lactate > 20 mM and pH <6.95Require lactate > 20 mM and pH <6.95

Equine Performance Equine Performance LaboratoryLaboratory

Sample collectionsSample collections– Blood – individual Blood – individual

venipuncture into venipuncture into lithium heparin lithium heparin tubes – plasma tubes – plasma harvested and harvested and stored at – 70 °Cstored at – 70 °C

– Urine – collected by Urine – collected by free catch method – free catch method – urine aliquotted and urine aliquotted and stored at – 70 °Cstored at – 70 °C

Sample distributionSample distribution– Samples are sent by Samples are sent by

overnight courier to overnight courier to participating participating laboratorieslaboratories

Process for sample Process for sample analysisanalysis ISO 17025 accredited laboratories usedISO 17025 accredited laboratories used Instrumentation is LC-MS or LC-MS-Instrumentation is LC-MS or LC-MS-

MS. MS. Develop and validate methods for each Develop and validate methods for each

analyte before testing experimental analyte before testing experimental samples. samples.

Schedule sample collection for a drug Schedule sample collection for a drug study after the proposed method has study after the proposed method has been suitably validated and approved been suitably validated and approved for use in the study.for use in the study.

Withdrawal Times Withdrawal Times ResearchResearch Priority Group Priority Group

11– AcepromazineAcepromazine– ButorphanolButorphanol– DetomidineDetomidine– GlycopyrrolateGlycopyrrolate– LidocaineLidocaine– MepivacaineMepivacaine– MethocarbamolMethocarbamol– PyrilaminePyrilamine

Priority Group Priority Group 22– BoldenoneBoldenone– DantroleneDantrolene– FirocoxibFirocoxib– FluphenazineFluphenazine– HydroxyzineHydroxyzine– NandroloneNandrolone– StanozololStanozolol– TestosteroneTestosterone

Glycopyrrolate Glycopyrrolate ExampleExample Quaternary amineQuaternary amine Anti-cholinergic Anti-cholinergic FDA approved as a pre-anesthetic FDA approved as a pre-anesthetic

but used in racing as a respiratory but used in racing as a respiratory “aid” due to bronchodilatory effect “aid” due to bronchodilatory effect and reduction in airway secretionsand reduction in airway secretions

Rapidly eliminated making Rapidly eliminated making detection more difficult detection more difficult

20-horse administration using 1 20-horse administration using 1 mg/horse IV and 10 mg/horse mg/horse IV and 10 mg/horse orally (n=6)orally (n=6)

Plasma Threshold

Time, hours Threshold concentration based on

99/95 Tolerance Interval

24 3.5 pg/mL

48 2.0 pg/mL

72 0.5 pg/mL

96 0.33 pg/mL

Firocoxib ExampleFirocoxib Example

Non-Steroidal Anti-Inflammatory DrugNon-Steroidal Anti-Inflammatory Drug FDA-approved for use in the horse as FDA-approved for use in the horse as

an oral paste an oral paste Drug has an exceptionally long half lifeDrug has an exceptionally long half life Clinical effects compare favorably to Clinical effects compare favorably to

phenylbutazone with fewer side effectsphenylbutazone with fewer side effects 20-horse administration using 0.1 20-horse administration using 0.1

mg/kg orally for 7 daysmg/kg orally for 7 days Merial funded the researchMerial funded the research

Firocoxib threshold Firocoxib threshold considerationsconsiderations Plasma concentrations after a single Plasma concentrations after a single

dose are less than those after a multiple dose are less than those after a multiple dosing regimen.dosing regimen.

Clinical effects are likely during a single Clinical effects are likely during a single dose administration. dose administration.

Therefore, a threshold must be able to Therefore, a threshold must be able to detect single dose administration. detect single dose administration.

A threshold of 20-50 ng/mL would detect A threshold of 20-50 ng/mL would detect race day administration of a single dose.race day administration of a single dose.

The withdrawal period after a multiple The withdrawal period after a multiple dosing regimen using a threshold of 40 dosing regimen using a threshold of 40 ng/mL is one week.ng/mL is one week.

Uniform thresholds Uniform thresholds and withdrawal timesand withdrawal times Other recommendations:Other recommendations:

– Methocarbamol threshold of 1 ng/ml in plasma, Methocarbamol threshold of 1 ng/ml in plasma, withdrawal guideline of 48 hours based on withdrawal guideline of 48 hours based on single 15 mg/kg IV dosesingle 15 mg/kg IV dose

– Anabolic steroid screening and confirmatory Anabolic steroid screening and confirmatory limitslimits

Drugs complete by our next Board meetingDrugs complete by our next Board meeting– AcepromazineAcepromazine– DetomidineDetomidine– LidocaineLidocaine– MepivacaineMepivacaine– PyrilaminePyrilamine

SOPs and method validation data will be SOPs and method validation data will be made available to all labs free of chargemade available to all labs free of charge

General Industry General Industry ChallengesChallenges Funding for RMTC to continue researchFunding for RMTC to continue research Funding from states for commissions to Funding from states for commissions to

increase spending on testing, increase spending on testing, investigatory capabilities, adjudicationinvestigatory capabilities, adjudication

““Silver bullet” thinking on complex issuesSilver bullet” thinking on complex issues Dealing with issues that may be strictly Dealing with issues that may be strictly

based on perception and misinformationbased on perception and misinformation Culture of medication useCulture of medication use Competition for horses which encourages Competition for horses which encourages

overnight extras instead of condition book overnight extras instead of condition book racesraces

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