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PostPosted: Wed Oct 07, 2015 12:33 pm 
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Motion received his first positive in his 23 years as a trainer. He will appeal the suspension for good reason...if nothing else to make a statement about the lax conditions around collection areas and improper research concerning drug withdrawal protocol. It is a "longshot" that they will overturn his suspension, but Motion feels it is worth appealing, considering the points brought up in the appeal need to be addressed and this could trigger the necessary conversation. Read the article below. TJ
http://www.bloodhorse.com/horse-racing/ ... n-positive


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PostPosted: Wed Oct 07, 2015 6:54 pm 
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Not racing, but here is the USEF document listing controlled and banned substances and their withdrawal times:

https://www.usef.org/documents/drugsmed ... es2013.pdf

According to that document, the therapeutic dose of methocarbamol is 5 g/450 kg body weight. Kitten's Point is a 3yo filly so we can probably assume that she is close enough for 450kg to work. Total blood volume for thoroughbreds is 10.31 L/100 kg body weight = 41 240 milliliters of blood. That means that the therapeutic dose for this horse is 121241 nanograms/mL. That translates to a decay half-life of 24.38%....after 1 hour, 24.38% of the drug is gone; after 2 hours, 24.38% of (1-0.2438)% of the drug is gone, and so on, until after 48 hours we have reached the threshold of 1 nanogram/mL (or 0.0008% of the original dose) remaining in the bloodstream.

So, here's where it gets interesting:

* With the above numbers, as little as a 1.5% variation in the withdrawal rate can be the difference between a negative test (>1 ng/mL) and a positive test (1.1 ng/mL).
* There appears to be a significant correlation between extended withdrawal times and method of administering the dose (oral vs. IM). (Source: http://www.caltrainers.org/publications ... report.pdf) If this is the case, then Motion is bang-on in appeal and challenging the standard for being not well-studied. That's a big, big, big deal.
* There also appears to be a significant correlation between extended withdrawal times and the drug administered with an NSAID such as bute. This is a 3yo filly....sounds like she may have tied up at some point? Again, if using the drug in a therapeutic way combined with another drug in a therapeutically appropriate setting leads to an extended withdrawal time of the first drug, and this is not well-studied and published, that's a big big big deal.

And that's leaving aside the arguments about clean lab and storage space, chain of custody, and whether or not the lab equipment is more sensitive and specific than had been previously.


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PostPosted: Thu Oct 08, 2015 4:25 am 
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Good post, thank you.

With the "size" (2.9n) of the overage and the suspected length of time between administration and test (7 days I believe) either the variability of withdrawal time guidance or the explanation put forth by Motion must be questioned. Remembering that Al Stall had a similar case a few years back (Sign in the Pocahantas I believe) I'd focus on the former.

It would be great if 3 or more states came together to run some comprehensive tests here on in-training animals here. Variables could should include:

-common interactions incl Lasix
-sex
-estrus
-IM/oral
-outdoor temp

At the very least the states with rules in effect should be forced to disclose sample sizes in the studies used to formulate their rules.


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PostPosted: Thu Oct 08, 2015 6:14 am 
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Quote:
With the "size" (2.9n) of the overage and the suspected length of time between administration and test (7 days I believe) either the variability of withdrawal time guidance or the explanation put forth by Motion must be questioned.


At 7 days out, I would be want to know if the dose was given orally along with Bute. Again, this is starting to sound like a 3yo filly who was tying up. Using a muscle relaxant with a painkiller would be an appropriate therapeutic regimen.

Then there's this: http://www.drf.com/news/drug-combinatio ... -positives

Quote:
According to Dr. Dionne Benson, the executive director of the Racing Medication and Testing Consortium, new research conducted by Dr. Mary Robinson at the University of Pennsylvania has indicated that bute is inhibiting the elimination of methocarbamol from the blood because both take the same chemical pathway to be eliminated from the body. Bute, in fact, takes precedent over methocarbamol, which is why the positives are returning overages for methocarbamol but not bute.

“Imagine you’re waiting on a metered ramp to get onto the highway, and this highway is the exit out of the body,” Benson said. “Only one can go out at a time, and the bute gets to go first.”


That article also says that the initial study on withdrawal times was done on 20 horses in a lab setting using only methocarbamol, not methocarbamol and bute together. In the article I posted last night, the California racing authorities tried looking at different strengths of Robaxin made a compounding pharmacies (where quality control is not as high, and the concentration of the drug varied) and found that the source of the drug was not significant and just paled in comparison to using Robaxin and bute.

If the above is true, that the guidelines for withdrawal times and the level of no further performance enhancing benefit was based on such a small sample in isolation, and this has happened repeatedly to other trainers in the last year (especially in DE and PA), and the new research from Penn says that the current guidelines are not adequate, I expect that regardless of whether Motion gets the judgement overturned, he's going to make a hell of a splash.

Edit to add: the mare is 5, not 3. Still sounds like a tie-up.

Edit to add 2: publishing lists of suggested withdrawal times and allowable thresholds is totally useless to trainers if the drug withdrawal times and allowable thresholds are unreliable and unreasonable. The medication in question is a muscle relaxant...therapeutic, not a performance enhancer. You can make a safety argument for other horses and jockeys, that the animal needs to have gotten to a threshold of no therapeutic benefit and no performance impact, but I can promise you that threshold is WAY higher the tabulated maximum allowable value. Having such low thresholds combined with such sensitive testing and such a poor sample upon which to base recommendations is edging into zero-tolerance territory, which sounds nice on paper but in the real world is asinine (e.g. a trace of banamine 5 days after a mild gas colic is just as bad an infraction as popping positive for cocaine!). If these rules are to have meaning--that they are meant for the safety of the public and integrity of the sport--then they need to be evidence-based and well-defined. Right now, they are not. Horse trainers and grooms and track officials are not pharmaceutical chemists and it's not reasonable to expect them to do that job....which means racing authorities need to step up.


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PostPosted: Thu Oct 08, 2015 3:42 pm 
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Hi CT,
It certainly is unusual, if administered 7 days out to find flunixin in the bloodstream...the only way flunixin would still be in the system after 7 days is if they administered the drug orally, or the IV dose was way above the allowed level. Pre-race drugs are usually and best administered IV. Doubt very much Motion would administer pre race meds orally with his pristine record, it's too risky? Makes sense CT, that something is wrong as you suggested below:

With the "size" (2.9n) of the overage and the suspected length of time between administration and test (7 days I believe) either the variability of withdrawal time guidance or the explanation put forth by Motion must be questioned..

RMTC guidelines (http://www.rmtcnet.com/resources/Flunix ... idance.pdf) suggest Flunixin is safely given 32 hours out given an IV dose of 1.1 mg/kg. I hope they can figure this out and overturn Motion's suspension...If I was in his shoes, I'd call you CT or Kimberly to plead my case:>)

The stacking of bute and flunixin would seem and is a proper therapy for a horse who ties up. Yet both these drugs were given as common practice in pre-race drug routines by many trainers. It was normal procedure by many just a few years ago to administer (IV) bute , (IV) flunixin and Dexamethasone (in the evening feed) prior to race day. Today they still try to incorparate these three, but are careful to follow withdrawal timelines which have changed drastically. Below is the RMTC guidelines for drug administration which might be of interest. TJ http://www.rmtcnet.com/resources/Contro ... 202014.pdf


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PostPosted: Thu Oct 08, 2015 5:34 pm 
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Hi TJ,

The medication overage was for methocarbamol, not flunixin. By the document you posted, it's 5 g orally or 15 mg/kg IV....which is a noticeable difference--for the archetypical 1000 pound horse, that's 7.5 g total for IV. I'd be interested to see what the documentation on the dose is and who drew it up. For an IV dose, that's not likely to be a groom, but a vet or a vet tech, and they'd keep records. If it was orally administered, I can see somebody using the IV dose orally....

....but for it to still be registering positive at a test that was 3 times the withdrawal time? And in a barn that was so notably clean and precise for so long, and where the trainer was very conservative with withdrawal times?

I doubt Motion will get the suspension overturned. After all the trainers in DE and PA got hosed by this rule, they're not going to overturn this for Motion. I do think that there will be a large influx of money and a lot of busy grad students at New Bolton pretty soon.


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PostPosted: Fri Oct 09, 2015 5:53 am 
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kimberley mine wrote:
Hi TJ,

The medication overage was for methocarbamol, not flunixin. By the document you posted, it's 5 g orally or 15 mg/kg IV....which is a noticeable difference--for the archetypical 1000 pound horse, that's 7.5 g total for IV. I'd be interested to see what the documentation on the dose is and who drew it up. For an IV dose, that's not likely to be a groom, but a vet or a vet tech, and they'd keep records. If it was orally administered, I can see somebody using the IV dose orally....

....but for it to still be registering positive at a test that was 3 times the withdrawal time? And in a barn that was so notably clean and precise for so long, and where the trainer was very conservative with withdrawal times?

I doubt Motion will get the suspension overturned. After all the trainers in DE and PA got hosed by this rule, they're not going to overturn this for Motion. I do think that there will be a large influx of money and a lot of busy grad students at New Bolton pretty soon.

Hi Kimberley,
Thanks for the correction, my bad....I think I had Rudy Rodriquez on my mind:>) Methacarbol or Robaxin has a suggested safe withdrawal time of 48 hours as opposed to the the drug I decided to give Motion the suspension for:>)...as stated in my error, Flunixin or banamine suggested WD of 32 hours.
As you said the overage is inconceivable given Graham's record...though it could have been a Vet error and the same horse was treated twice...or maybe three times in this case:>)
Concerning the documentation on the dose and who drew it up....this update was just released from the RMTC in defense of their research. You should find it of interest. TJ http://www.bloodhorse.com/horse-racing/ ... -threshold


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PostPosted: Fri Oct 09, 2015 7:16 am 
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I saw that, and while I can't access the article, I still keep coming back to, this was a single study on 20 horses of a single dose.

This blog article has more thoughts on the matter, with references:

http://musingsonequinemedicine.blogspot ... chive.html

I am reminded of Lucy, Charlie Brown, and the football.


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PostPosted: Fri Oct 09, 2015 8:17 am 
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kimberley mine wrote:
I saw that, and while I can't access the article, I still keep coming back to, this was a single study on 20 horses of a single dose.

This blog article has more thoughts on the matter, with references:

http://musingsonequinemedicine.blogspot ... chive.html

I am reminded of Lucy, Charlie Brown, and the football.

Hi Kimberley,
Thanks, interesting blog. Seems like RMTC will keep shooting themselves in the foot even as they try to get the industry in line with drug protocol. It's obvious there is a problem as Motion and his mentor Jonathan Sheppard both were issued rare suspensions due to Methocarbamol overages. Motions came almost 1 year after Sheppard's 2nd positive for Methocarbamol, so maybe that triggered Motion's decision to dispute the findings. Sheppards story: http://www.theracingbiz.com/2014/08/15/ ... xin-cases/
They mentioned flunixin (in the blog) as another possible error and I mentioned Rudy Rodriquez who had 3 or 4 positives in a row for flunixin. Rudy's stories: (1) http://www.drf.com/news/rudy-rodriguez- ... e-flunixin
(2) http://www.bloodhorse.com/horse-racing/ ... -positives
RR isn't a fool and he wouldn't keep trying to break the rules that many times and keep getting caught. Starting to look more and more like they don't have the proper protocol's in place for many of the drugs. One of the worst things is that it takes so long to get test results back. I guess in Rudy's case, he could have been using the same protocol which happened to be wrong all along while awaiting results and that could be why he had so many flunixin positives? It certainly is a mess and the more these big name trainers get caught in the process I think we will see some positive changes. Even Billy Mott received a flunixin suspension which he is appealing. Mott's story http://www.drf.com/news/hall-fame-train ... suspension ....TJ


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PostPosted: Fri Oct 09, 2015 7:44 pm 
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My most charitable interpretation: I think the RMTC wants on some level to do the right thing, but they value their public image far more than they value doing the right. The right thing, in this case, is an evidence-based testing protocol that uses good science and good methods as well as uniform standards, uniform laboratory protocols (!!!), and even designated labs nationwide. They started out with good intentions and a lot of press, but now that they have been shown to be unprepared and doing sloppy work, they are in damage control mode.

Unfortunately, their idea of damage control mode is to claim that their studies are right, they have to be, rather than question whether their studies are adequate. A study can be 100% factually correct and still not be adequate to answer the original question, or be totally irrelevant to the question at hand.

I don't know if you have heard of Mythilus, who was disqualified from the 2008 Olympics after testing positive for trace amounts of an anti-inflammatory that is used in Asia, but not in North America. His US-based rider was suspended and banned from FEI competition as a result. The FEI tribunal itself agreed with the rider's argument that the horse had picked up environmental contamination when it was taken to a vet hospital in Hong Kong for a legitimate veterinary emergency....but under their "no fault, no negligence" policy, because she could not prove beyond a shadow of a doubt that it was environmental contamination, she was suspended and the entire US team booted from the Team Dressage competition. http://www.fei.org/system/files/24%20-% ... t%2008.pdf

Stuff like this makes me want to beat my head against the wall. It doesn't do anything to keep folks from doping, because the ones who are successfully doping are using things that don't show up on the formulary list (see Lance Armstrong). It is also bad science and that really upsets me, as I'm sure you figured out on the first reply I made to this post. :)


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PostPosted: Fri Oct 09, 2015 8:49 pm 
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kimberley mine wrote:
My most charitable interpretation: I think the RMTC wants on some level to do the right thing, but they value their public image far more than they value doing the right. The right thing, in this case, is an evidence-based testing protocol that uses good science and good methods as well as uniform standards, uniform laboratory protocols (!!!), and even designated labs nationwide. They started out with good intentions and a lot of press, but now that they have been shown to be unprepared and doing sloppy work, they are in damage control mode.

Unfortunately, their idea of damage control mode is to claim that their studies are right, they have to be, rather than question whether their studies are adequate. A study can be 100% factually correct and still not be adequate to answer the original question, or be totally irrelevant to the question at hand.

I don't know if you have heard of Mythilus, who was disqualified from the 2008 Olympics after testing positive for trace amounts of an anti-inflammatory that is used in Asia, but not in North America. His US-based rider was suspended and banned from FEI competition as a result. The FEI tribunal itself agreed with the rider's argument that the horse had picked up environmental contamination when it was taken to a vet hospital in Hong Kong for a legitimate veterinary emergency....but under their "no fault, no negligence" policy, because she could not prove beyond a shadow of a doubt that it was environmental contamination, she was suspended and the entire US team booted from the Team Dressage competition. http://www.fei.org/system/files/24%20-% ... t%2008.pdf

Stuff like this makes me want to beat my head against the wall. It doesn't do anything to keep folks from doping, because the ones who are successfully doping are using things that don't show up on the formulary list (see Lance Armstrong). It is also bad science and that really upsets me, as I'm sure you figured out on the first reply I made to this post. :)

Hi Kimberley,
Wow...what a terrible situation that was. Seems like they too had a pristine record, but absolute responsibility falls on the horses connections no matter what the circumstances surrounding the positive. So I guess Motion and Mott might take a little vacation?
I have to agree with your opinion of the RMTC, who seem to be in over their head at this point. I know many more racing jurisdictions have signed on to follow their recommendations....but the RMTC has to be willing to scrutinize their work under situations like this and use some common sense judgement if their withdrawal times should be re-visited? Since their science doesn't seem to be up to par:>) TJ


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PostPosted: Sat Oct 10, 2015 10:32 am 
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Hi TJ,

The FEI is a treasure trove on horror stories related to medication rules violations. Here's a doozie:

http://www.fei.org/system/files/2014-CM ... 202015.pdf

Quote:
That in light of the concentration found in the B Sample, the Acepromazine – assuming that it had been administered at the standard dose of 0.15 mg/kg – would have been administered about 30 to 40 hours prior to the sampling, i.e. during the night of Wednesday 27 to Thursday 28 August 2014. That during this period of time the stables were closed and that therefore he had no access to the stables. Specifically that riders and their teams were not allowed to access boxes from 11 pm to 6 am, and that therefore it had been physically impossible for him and any members of his team to administer the substance to the Horse....

...That in addition, two weeks prior to the Event, all products administered to the Horse had been checked by the French National Team, in order to ensure that they did not contain any Prohibited Substances. That special foods, guaranteed to not contain any traces of Prohibited Substances, had also been purchased specifically for that purpose. That he had taken any measures necessary to prevent any risk of contamination, and that he could not have watched the Horse during closing hours of the stables.


Emphasis mine.

The rider was found guilty and banned for 6 months.

I am sure that somebody on Motion's legal team is going to bring this up with regards to sample control and security.


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