All About Salbutamol

[veganrob]

Re: Re:

If he made that claim, I think the response might be, you must have taken a lot of extra puffs, and if you needed that much salbutamol, you must have had a very severe attack, why didn’t you use a nebulizer?

That's assuming they had one to hand though, are nebulizers regularly carried by teams ? How big / portable are they ?

Very small and portable

 

[Red Rick]

Antibiotics for infections that are 80 viral.

I guess that bit is common

 

[yaco]

Hope Sky can find a record of the aforementioned antibiotics - After all record keeping is not their strongest suit.

 

[Robert5091]

Antibiotics? ... now we're getting somewhere. Let's float that one out there
(Remember Froome has that unique multiple tour winner physique)

 

[Merckx index]

I already discussed a possible defense based on use of antibiotics upthread, beginning two weeks ago. The first post linked below cites the key study, the second lays out the possible defense:

viewtopic.php?f=20&t=33768&p=2220840&hilit=antibiotics#p2220840
viewtopic.php?f=20&t=33768&p=2221744&hilit=antibiotics#p2221744

If I figured this out, I'm not surprised one of Froome's scientific advisors did. To repeat, a very recent study (in press) reported that many antibiotics can inhibit the same organic cation transporters (OCTs) used to excrete salbutamol:

http://sci-hub.la/10.1016/j.ejps.2018.01.002

Under these conditions, the kidneys don't store the salbutamol, it just remains in the circulation in higher concentrations than normally would be the case. If one stops taking the antibiotic, the inhibition would be relieved, and the higher levels in the blood would mean higher than normal levels excreted.

Since this research is so new, though, there presumably have been no studies directly demonstrating inhibition of salbutamol excretion. With the known data, one at best could make an estimate of the degree of inhibition of salbutamol excretion, and from there, how high the plasma level of the drug. It quickly gets very complicated, though, because as plasma levels of the drug rise, the salbutamol more effectively competes with the antibiotic for the transporter. IOW, I would expect a plateau in plasma salbutamol level. This would all be based on theory, unless they actually tried to reproduce it in the lab. If they did, they could probably publish the results, as it would be a novel research finding. Right after the passage quoted by thehog:

”That’s not something I’ve come across in the literature,” says Dr John Dickinson, head of the respiratory clinic at the University of Kent and the UK’s foremost expert on asthma in sport.

Of course, they would also have to provide evidence that Froome was taking the antibiotic prior to the AAF (not at the same time, as Walsh says), showing its use was correlated with lower levels of excreted salbutamol, and that the level spiked shortly after he stopped taking the antibiotic. He might be able to demonstrate levels of the antibiotic in the urine, though as I noted before, one of the most promising candidates, erythromycin, is mostly excreted by the liver. There is also the issue of why this has not occurred in the past with riders taking antibiotics.

 

[70kmph]

Rabin talks about this also

Is there specific knowledge of the factors that cause excretion (the action by which the body discharges a substance) to evolve from salbutamol?

I would be wary of considering all possible pharmacological, toxicological or physiological cases where there may be interference with the renal excretion of a substance or its metabolism. It is enough that you have taken another substance that goes through the same cytochrome P-450 [organic molecule involved in the biodegradation of exogenous molecules, including salbutamol] : it can have an effect on the excretion time. At the renal level, there may also be a substance that interferes with excretion. But we do not rely on assumptions. We want facts.

 

[thehog]

Re:

Rabin talks about this also

Is there specific knowledge of the factors that cause excretion (the action by which the body discharges a substance) to evolve from salbutamol?

I would be wary of considering all possible pharmacological, toxicological or physiological cases where there may be interference with the renal excretion of a substance or its metabolism. It is enough that you have taken another substance that goes through the same cytochrome P-450 [organic molecule involved in the biodegradation of exogenous molecules, including salbutamol] : it can have an effect on the excretion time. At the renal level, there may also be a substance that interferes with excretion. But we do not rely on assumptions. We want facts.

Facts? who needs facts when there is David Walsh?

 

[Merckx index]

Re:

Rabin talks about this also

Is there specific knowledge of the factors that cause excretion (the action by which the body discharges a substance) to evolve from salbutamol?

I would be wary of considering all possible pharmacological, toxicological or physiological cases where there may be interference with the renal excretion of a substance or its metabolism. It is enough that you have taken another substance that goes through the same cytochrome P-450 [organic molecule involved in the biodegradation of exogenous molecules, including salbutamol] : it can have an effect on the excretion time. At the renal level, there may also be a substance that interferes with excretion. But we do not rely on assumptions. We want facts.

While antibiotics like erythromycin have been shown to inhibit P450, I don't think a defense based on P450 is as strong as one based on transporters. In the first place, while P450 is present in the lungs, apparently very little salbutamol is metabolized there. So most salubutamol metabolism following inhaling occurs on that portion of the drug that is accidentally swallowed. And for that portion, more of it is metabolized via sulfation and glucoronidation than via P450. Of course, it's possible the two effects could combine. But as you (or are you quoting Rabin? link?) say, those are just assumptions.

http://dmd.aspetjournals.org/content/39/5/864.long

It could get wild if Froome's team requested a very long delay in order to carry out a study supporting their theory. That would definitely push the hearing and final decision past the TDF. I wonder if any athlete has ever tried that before.

 

[Merckx index]

Re: Re:

Yes, the lawyers or 'experts' for Froome's defense probably got the antibiotics idea from the Rabin interview in December

No, Froome has scientific experts working for him, I expect they came up with this idea on their own. The evidence that antibiotics can affect P450 catalysis has apparently been around for quite a while, and while AFAIK their effect on transporters is literally hot off the presses, they surely would have considered inhibition of transporters by something. The bottom line is that anything Rabin is aware of, Froome's advisors should also know about. Rabin, after all, is not a specialist, he oversees all kinds of doping cases.

From the Matzka case judgment :

Picking the most likely among several very improbable scenarios is not what the UCI ADR are looking for: there needs to be an objective evaluation... the UCI has indeed a duty to collaborate – which it has done in the present proceedings by conducting own research and calling an expert witness – and not simply to leave the Rider with the insurmountable task of disproving several hypothetical scenarios... Thus, while the Single Judge accepts the Rider’s submission that his task is to put forward an objectively credible scenario, it does not accept the argument that the UCI needs to bring forward a doping scenario which is more likely to have happened.

This passage doesn’t make much sense to me. First it says “UCI has indeed a duty to collaborate” and not “leave the Rider with the insurmountable task of disproving several hypothetical scenarios”, but then it denies “that the UCI needs to bring forward a doping scenario which is more likely to have happened.” If the UCI does not promote a specific scenario, how can the rider not be left with the task of disproving several hypothetical scenarios?

What Froome has to do is provide evidence for his theory, then show that on the basis of that evidence, that theory is more plausible than alternatives. I don’t see how that process doesn’t involve discussing and in effect disproving several alternatives.

Froome has something to prove such that the Judge will accept his explanation to be more likely true than false. That will be hard if his explanation depends on multiplication of several factors, each of which is independently improbable. And meanwhile, the UCI doesn't have to prove that the salbutamol positive occurred some other way.

A lab test can establish how improbable the scenario is. The lab test should demonstrate that while Froome is on antibiotics, his plasma levels of salbutamol rise and his urine levels fall, compared to when he's not on antibiotics. If he can establish that, the second step is to provide evidence that he actually took antibiotics during a time frame that is consistent with his salbutamol levels during the Vuelta.

If necessary, the UCI could just have Froome's samples tested for antibiotics, and if there are none found, to avoid the whole theoretical discussion.

But if he took an antibiotic such as erythromycin that is mostly metabolized then excreted by the liver, urine levels might be too low to detect (that is another point the lab test could address). What would really be helpful would be blood samples. It’s possible Froome was singled out for a passport test at some point during the Vuelta. At a minimum, of course, if he’s going to claim he was on antibiotics, he at least needs to provide a prescription dated at that time. That would not be as compelling as detection in bodily fluids, but certainly better than nothing.

 

[Robert5091]

Froome/Sky would happily pay a fine and keep riding ... just give 'em the 2 mill Euro and call it quits?

Whoever is the Judge I would suggest staying off a mobile phone - the Murdochs have a history you know (SDB did panic one time too I recall)

 

[Red Rick]

To what degree does it matter legally that the Froome team are juggling theories and basically reverse engineering the story?

 

[King Boonen]

Re:

To what degree does it matter legally that the Froome team are juggling theories and basically reverse engineering the story?

Do we know they are doing that? There's loads of supposition about what's going on based on what evidence can be found but we don't really know do we?

Either way, I don't think it matters. As others have pointed out, they just need to show that those values are possible to hit within usage guidelines in a way that could happen. The could will be the main argument if they manage it I would think.

 

[yaco]

Re: Re:

Any subsequent case heard at CAS after a hearing at an Anti-Doping Tribunal is always a 'DE Novo' case which means a completely new trial - So in other words fresh evidence and tactics.

Froome's defense can try something different on appeal to CAS, but UCI will have submitted the judgment and reasoning of Anti-Doping Tribunal to CAS, when and if those proceedings begin. So, for Froome's lawyers to contradict their original claims, would make them look more confused at CAS. Different approach to the same UCI evidence, except from a worse standing point, having already been found guilty.

CAS appeal would be more likely to get Froome's ban reduced in duration, than to clear him completely.
Also, depends whether Froome has already admitted responsibility on paper, or whether his defense has contended complete innocence. Maybe deny responsibility at Anti-Doping Tribunal (meaning he gets banned for two years), then admit it at CAS, in hopes of getting a reduced ban. Or 'double down' on a losing gamble, who knows...

A De Novo hearing means that both sides can produce new evidence, different specialist witnesses, run different angles etc, etc, etc - It's not like pre 2015 when an appeal was strictly on a point of law etc from the original hearing - Think of it as a completely new hearing and that the first hearing never happened.

 

[Wiggo's Package]

Re:

To what degree does it matter legally that the Froome team are juggling theories and basically reverse engineering the story?

Good question

Of course we don't know the Froome team are doing that for sure. But the possibility will not escape the ADT judge or the CAS judges if it gets that far. These people aren't stupid

And with an AAF the onus is on the Froome team to positively prove with robust evidence (including the Dawg in a lab) why their guy tripped the wire. Scatter gunning blacmange at the wall simply doesn't cut it. Unless you get lucky and find a procedural **** up. But that's a technicality. Lizzie just got lucky, right

In that context the reverse engineered the juggling theories approach shouldn't sway the judge. Maybe it's a tactic designed for the fanboys. And the gullible journalists like Walsh

But surely Brailsfraud/Sky wouldn't prioritise PR above all else. That would play against type

 

[AussieGoddess]

Re: Re:

Any subsequent case heard at CAS after a hearing at an Anti-Doping Tribunal is always a 'DE Novo' case which means a completely new trial - So in other words fresh evidence and tactics.

Froome's defense can try something different on appeal to CAS, but UCI will have submitted the judgment and reasoning of Anti-Doping Tribunal to CAS, when and if those proceedings begin. So, for Froome's lawyers to contradict their original claims, would make them look more confused at CAS. Different approach to the same UCI evidence, except from a worse standing point, having already been found guilty.

CAS appeal would be more likely to get Froome's ban reduced in duration, than to clear him completely.
Also, depends whether Froome has already admitted responsibility on paper, or whether his defense has contended complete innocence. Maybe deny responsibility at Anti-Doping Tribunal (meaning he gets banned for two years), then admit it at CAS, in hopes of getting a reduced ban. Or 'double down' on a losing gamble, who knows...

A De Novo hearing means that both sides can produce new evidence, different specialist witnesses, run different angles etc, etc, etc - It's not like pre 2015 when an appeal was strictly on a point of law etc from the original hearing - Think of it as a completely new hearing and that the first hearing never happened.

While a De Novo hearing is indeed a completely new trial, where the legal team are free to pursue a different line of reasoning or defence ... it certainly is not 'as if the first hearing never happened'. They cannot give conflicting evidence.

 

[Robert5091]

Re: Re:

Froome/Sky would happily pay a fine and keep riding ... just give 'em the 2 mill Euro and call it quits?
Whoever is the Judge I would suggest staying off a mobile phone - the Murdochs have a history you know

The monetary fine at the Anti-Doping Tribunal is only if the Rider was found responsible for their Rule Violation (and proved to have done it intentionally) and it isn't an option in exchange for not getting banned ...
it would be both getting banned for two years, AND fined an amount equal to net income from cycling, in the year the Rule Violation occurred. So in court, the rich riders can't buy their way out of a ban, by paying off the UCI with a big fine.

And bribery of these particular Judges is not likely either, given the way the judgments are published, and referenced in journals and books and academic law conferences. It's like a whole ongoing field of sports law, and they have their professional reputations to maintain, among their colleagues. Actually some of the Judges might see putting Froome away as a prestigious accomplishment

Biased judge? Case dismissed!

The telephone reference was to bugging - not bribery. Any dirt in a judge's past might "surprisingly" become public ...
A big fine? No ... though a donation or two to the UCI might help?

 

[yaco]

Re: Re:

Any subsequent case heard at CAS after a hearing at an Anti-Doping Tribunal is always a 'DE Novo' case which means a completely new trial - So in other words fresh evidence and tactics.

Froome's defense can try something different on appeal to CAS, but UCI will have submitted the judgment and reasoning of Anti-Doping Tribunal to CAS, when and if those proceedings begin. So, for Froome's lawyers to contradict their original claims, would make them look more confused at CAS. Different approach to the same UCI evidence, except from a worse standing point, having already been found guilty.

CAS appeal would be more likely to get Froome's ban reduced in duration, than to clear him completely.
Also, depends whether Froome has already admitted responsibility on paper, or whether his defense has contended complete innocence. Maybe deny responsibility at Anti-Doping Tribunal (meaning he gets banned for two years), then admit it at CAS, in hopes of getting a reduced ban. Or 'double down' on a losing gamble, who knows...

A De Novo hearing means that both sides can produce new evidence, different specialist witnesses, run different angles etc, etc, etc - It's not like pre 2015 when an appeal was strictly on a point of law etc from the original hearing - Think of it as a completely new hearing and that the first hearing never happened.

While a De Novo hearing is indeed a completely new trial, where the legal team are free to pursue a different line of reasoning or defence ... it certainly is not 'as if the first hearing never happened'. They cannot give conflicting evidence.

I personally think ' De Novo ' hearings are rubbish because it is in effect double jeopardy - Any appeal should be based purely on 'points of law' arising from the original hearing

 

[EricDolphy]

I've always wondered how consistent a dose you might get from asthma enhalers. Research would suggest it depends on your shaking technique.

http://online.liebertpub.com/doi/abs/10.1089/jamp.2015.1284?journalCode=jamp

Results: All of the suspension pMDIs produced variable amounts of drug over the shake-fire delays tested. A comparison of the delivered doses after the 0- and 60-second delays showed that the drug delivered increased for the Flovent HFA (320%), Ventolin Evohaler (346%), and Airomir Inhaler (230%) pMDIs;

It just seems more likely that Chris was getting variable doses from his medical equipment than having a kidney issue.

 

[Robert5091]

Re:

I've always wondered how consistent a dose you might get from asthma enhalers. Research would suggest it depends on your shaking technique.

http://online.liebertpub.com/doi/abs/10.1089/jamp.2015.1284?journalCode=jamp

Results: All of the suspension pMDIs produced variable amounts of drug over the shake-fire delays tested. A comparison of the delivered doses after the 0- and 60-second delays showed that the drug delivered increased for the Flovent HFA (320%), Ventolin Evohaler (346%), and Airomir Inhaler (230%) pMDIs;

It just seems more likely that Chris was getting variable doses from his medical equipment than having a kidney issue.

There you go - case dismissed! (PS - sue the inhaler maker too!)

 

[EricDolphy]

Re: Re:

There you go - case dismissed! (PS - sue the inhaler maker too!)

Inadvertant doping -> strict liability -> guilty

 

[Random Direction]

Re:

I've always wondered how consistent a dose you might get from asthma enhalers. Research would suggest it depends on your shaking technique.

http://online.liebertpub.com/doi/abs/10.1089/jamp.2015.1284?journalCode=jamp

Results: All of the suspension pMDIs produced variable amounts of drug over the shake-fire delays tested. A comparison of the delivered doses after the 0- and 60-second delays showed that the drug delivered increased for the Flovent HFA (320%), Ventolin Evohaler (346%), and Airomir Inhaler (230%) pMDIs;

It just seems more likely that Chris was getting variable doses from his medical equipment than having a kidney issue.

Great first post. Love the additional variable -could have been this, ciuld have been that. Chewbacca Defense. Working hypotheisis is cyclists dope to imprive performace, and try to do so in grey areas. Froome mainlining salbutamol is no differenr. That he shook his kidneys the wrong way and got busted isnt going to fly.

 

[Catwhoorg]

The key is the aggregation of marginal doubts

 

[gillan1969]

Re:

The key is the aggregation of marginal doubts

well...from the quote on the BBC website Froome is hoping that people will see it from his "point of view"

facts tend not to be 'points of view'

"the facts say i took more than I was allowed...I say i didn't"

 

[brownbobby]

Re: Re:

The key is the aggregation of marginal doubts

well...from the quote on the BBC website Froome is hoping that people will see it from his "point of view"

facts tend not to be 'points of view'

"the facts say i took more than I was allowed...I say i didn't"

Its clear, to me at least when read in context with the full article, that in this quote he's referring to his right to continue riding whilst the case is pending. Not about the test results. Which puts a different spin on the quote to the one you suggest

 

[gillan1969]

Re: Re:

The key is the aggregation of marginal doubts

well...from the quote on the BBC website Froome is hoping that people will see it from his "point of view"

facts tend not to be 'points of view'

"the facts say i took more than I was allowed...I say i didn't"

Its clear, to me at least when read in context with the full article, that in this quote he's referring to his right to continue riding whilst the case is pending. Not about the test results. Which puts a different spin on the quote to the one you suggest

i would disgaree...the 'facts' of the process are already out there....they are the....eh...process he's in - we know those

what's not out there are the 'facts' of his case...i.e. his defence