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All About Salbutamol

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What will the verdict in Froome's salbutamol case?

He will be cleared
43
34%
3 month ban
4
3%
6 month ban
15
12%
9 month ban
24
19%
1 year ban
16
13%
2 year ban
21
17%
4 year ban
3
2%
 
Total votes : 126

Re: Re:

15 Dec 2017 18:13

Merckx index wrote:There have been attempts to distinguish the two by tests, but one problem is that in the process of inhaling, people apparently do swallow some of the drug.


This was actually a reason that Pettachi used in his defence. He was using his inahler during the race which I assume would make it easier to misuse the inhaler as opposed to just sitting down.
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Re: All About Salbutamol

15 Dec 2017 19:56

Page 122 & 123 in https://t.co/swGGi22V8P has a nice summary review of the systemic effects of salbutamol. Combined with the fat burning properties, this is ubiquitous drug could pack quite a punch. Oral during off-season to drop the christmas pud, then inhale during the season and races to increase cardio-vascular output while always keeping below the 1000 limit at race day testing window time.
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Re: All About Salbutamol

15 Dec 2017 21:14

thehog wrote:Froome’s hydration GSK testing, its on the low side.

Image

Yeah, the guy is a beast in scorching heat, how would he have dehydration issues at 20 degrees?
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Re: All About Salbutamol

16 Dec 2017 01:47

Here’s a summary of the Froome case as I see it.

1. I think it’s quite unlikely he will be able to explain his high urine level of salbutamol as the result of inhaling the drug within the allowable limits. I have not seen a single study reporting a level that high, 2000 ng/ml., for any subject taking the maximum amount allowed, 1600 ug, within 24 hours. One study, discussed here, found a few subjects with amounts higher than this when the entire 1600 ug was inhaled at once, but since there’s also a limit of 800 ug in twelve hours, this would not be allowed. Other studies, in which the drug is taken over some period of time, report an occasional subject above the threshold of 1000 ng/level, but just barely. While I haven’t seen every study, and I’m not going to claim a level of 2000 ng/ml can never occur under allowable conditions, based on the data I have seen, which include mean levels and standard deviations for a pool of subjects, I’m fairly confident that a level as high as Froome’s would be exceptionally rare. And it should be. The WADA threshold is intentionally set at a level to minimize false positives, so it should be difficult for a rider inhaling the allowed amount to exceed it, let alone to produce a value double the threshold.

(Edit: I just started looking at the Sundby CAS case linked upthread. It turns out the athlete took nearly ten times the amount of allowed salbutamol, via a nebulizer. So hardly surprising that he exceeded the threshold. His argument apparently is that it was medically necessary, and that since it was administered orally, would not have been performance-enhancing. I also bring this up because it further supports my point, below, that it's possible to take a much larger than allowed dose and not exceed the threshold. This athlete's urine level was actually lower than Froome's, despite taking 15 mg of salbutamol in a period of just a few hours.)

There has been speculation that his level might have resulted from dehydration, which concentrates solutes in the urine. But I don’t think that explanation will work, either, for three reasons. First, even a study which attempted to maximize dehydration, by minimizing water intake of subjects during exercise, found urine levels of salbutamol as high as or higher than Froome’s only under conditions that exceed the allowable intake of the drug.

Second, during a race, riders of course attempt to remain fully hydrated, so while some dehydration is certainly likely, I don’t think it would be to the extreme reported in that study. Also, as will be discussed further below, Froome tested below the threshold literally more than a dozen times during the Vuelta. If dehydration could make that much difference in his values, surely he would have exceeded the threshold more than once.

Third, the WADA guidelines specify how much the threshold level and decision limit are to be raised if the specific gravity of the urine is higher than normal levels. So I assume that if Froome’s urine was concentrated as a result of dehydration, that correction would have been made. If it was, and the adjusted threshold and limit were now higher than Froome’s level, then he would not have an AAF, and we never would have heard about this.

(Edit: In that same CAS decision mentioned above, it's stated that "WADA do not allow a correction for SG down to 1020 for exogenous substances with a threshold such as Salbutamol." So apparently Froome's values could have been affected by dehydration without WADA doing anything about it. I now see further, from the passage that hog quotes below, that the reason WADA doesn't do anything is because they have an allowable range of urine SG values. If the athlete's urine SG falls within this range, they go ahead with the test. If it doesn't, they request another sample. As hog points out, since Froome's sample was actually analyzed, the SG must have fallen within the required range. Depending on how broad the range is, Froome's value at 1.020 might have been considerably lower, but probably not below the threshold, and even if were, this won't help him. All he can do in a further test is try to maximize dehydration to the point that it affects his urinary value, but does not take the SG out of the allowed range).

2. How did Froome come to have such a high level of salbutamol? This is puzzling, because he was tested before and after the one day, stage 18, in which this level was reported, without as far as we know having any other tests in which the level was above the allowed threshold. In fact, he wore the leader’s jersey in the Vuelta from stage 3 to the end of the race, which means, I believe, that he was tested fifteen times before stage 18, and three times after. Any explanation has to take this into account, and in particular, it seems to indicate he wasn’t intentionally taking large, unallowed doses of salbutamol throughout the race. But I will return to this point later.

There seem to be only two possible explanations. The first is that he took more than the allowed dose, either by accident or intentionally. The problem with this scenario is that he would have had to exceed the allowed dose by a very large amount. Since he wasn’t above the threshold of 1000 ng/ml following any of the other stages, the amount that he took on stage 18 appears to have been more than double what he normally took. (Note to hazaaran: the data fully back up the assumption of roughly linearity in this range). I think it’s unlikely that such a large difference would result from an accident or carelessness. In fact, based on the studies I’ve seen, he would have to take considerably more than the allowed amount just to get to the threshold. According to one typical study, an 8 mg oral dose might be expected to result in a peak urine level of roughly 2000 ng/ml. Thus about 4 mg would be needed to breach the threshold of 1000 ng/ml. These relationships are roughly the same for inhalation.

One might point out that Froome’s urinary level of salbutamol would depend not only on how much of the drug he took, but when. If he took much of the drug before the stage began, and urinated at some point during the stage, his level when tested at the end of the stage would be relatively low. Whereas if he took much of the drug during the stage, particularly late in the stage, and didn’t relieve himself, his levels would be much higher. The problem, though, is that even if we presume his stage 18 level occurred under something like the latter conditions, resulting in maximally high urine levels, this level is still far above what would be expected if he inhaled the maximum allowable. This is clear from the numbers I provided in the preceding paragraph. His level doesn’t make sense as the result of accidentally taking somewhat more than his usual dose, even if everything he did subsequently maximized the amount of drug found in the urine test.

3. However, there is another version of this explanation where these factors may become relevant. Suppose that Froome was in fact taking larger than allowed doses of salbutamol throughout the Vuelta. He would probably be doing this as an intentional doping program, but for our purposes, it doesn’t really matter why. The conventional thinking is that he couldn’t have been doing this, or he would have tested above the threshold on other stages besides 18. But this is not necessarily the case.

I already pointed out the CAS Sundby case, in which the athlete took 15 mg of salbutamol, and didn't exceed the threshold by that much, 1300 ng/ml. In fact, WADA stated in the decision that had Sundby took that amount over 24 hours (he actually took it within five hours), he probably would not have exceeded the threshold! I also noted that a study reported that a 4 mg oral dose resulted in a peak urine level right about at the threshold of 1000 ng/ml. So while taking that much might be pushing the envelope, Froome could probably take a somewhat lower dose, say 2 mg, without concern. That alone might give him some benefit that he thought made it worthwhile.

But he could take more if he was careful about the timing. About half of an oral dose of salbutamol is excreted within 3-4 hours after ingestion. Most stages are longer than this, of course, so if Froome were to take a very large dose before the stage, then urinate at some point before the end of the stage, he could reduce his urinary levels substantially. That 4 mg borderline dose might now become as much as 8 mg, and a safe dose now becomes perhaps 5-6 mg.

Now it becomes somewhat easier to understand how one stage could have an outlier value. Part of the reason could be because he took more than the usual dose before the stage began, either intentionally or by accident. Part of the reason could be because he didn’t pass urine before the end of the stage, or conversely, did so too soon after dosing. Part of the reason could be because in addition to an oral dose at the start of the stage, he also inhaled the drug during the stage, more so than he anticipated.

All of these factors, contributing together, make it somewhat easier to see how Froome might have greatly exceeded the limit. I’m not saying this is a completely satisfactory solution, the difference between stage 18 and other stages is still huge, but I think it’s more credible than the alternative version, in which he simply inhaled too much by accident. At the very least, I think it establishes that it would be possible to take fairly large doses of salbutamol, and generally remain under the threshold. And most important, this is a testable hypothesis; it might be supported by further data that should be available. This scenario predicts that Froome's urinary values on the other stages would be fairly high, > 500 ng/ml, probably higher than one would expect if he was just inhaling the allowed amount. WADA, of course, only cares if his values are below the threshold, but in theory, if Froome was taking large oral doses of salbutamol, there should be a disconnect between his claims of inhaled doses and his actual urinary levels. If this case gets as far as CAS, I can see that issue becoming important.

Also, someone help me out here. Are nature breaks common in GT stages? I know they happen sometimes, but would a rider usually stop at some point? Because with a relatively rapidly cleared drug like salbutamol, whether or not you stopped to piss before the end of the stage could be critical.

And while on this general subject, I asked earlier what evidence there was that Froome used salbutamol previously. All I got in response was that he used an inhaler in 2014. But that's after the great transformation! What about before? Again, this seems to me fairly critical.

4. The other explanation for his high level is that it was the result of a blood transfusion. He had salbutamol in his circulation—the result of intentional doping with probably oral dosing—when he withdrew blood, and when he then transfused this blood, during the Vuelta, the salbutamol of course went into his system as well, and resulted in exceeding the threshold. This explanation has the advantage of accounting for why Froome exceeded the threshold only once—he transfused before the stage—and of course, blood transfusion is a very well established means of performance enhancement, much better supported than simply using salbutamol. In this scenario, salbutamol would probably be a secondary means of doping, not the main factor, and he wasn't necessarily using it all during the Vuelta, except for inhaling it.

This explanation also has problems, though. First and foremost, in order for a transfusion to contain enough salbutamol to result in a urinary level exceeding the threshold, an extremely high dose would have to have been taken prior to blood withdrawal. How high? Pharmacokinetic studies of salbutamol, in which peak plasma concentrations of the drug are determined following an oral dose, indicate that a maximum as high as 120 ng/ml. might result from 4 mg. Since 500 ml of blood contains roughly 300 ml of plasma (the remainder is the hematocrit), this would contain about 36 ug of salbutamol, or roughly 1% of the oral dose.

As I pointed out above, an 8 mg oral dose is roughly the minimum one would have to take to result in a peak urinary level of salbutamol of 2000 ng./ml, the threshold concentration. From this it follows that for 500 ml of transfused blood to contain enough of the drug to reach this threshold, the dose preceding withdrawal would have to be about 800 mg, or nearly 1 g! This is a very rough estimate, and might be reduced somewhat by taking into account other considerations. For example, only about half of an oral dose gets into the circulation, whereas of course all of the drug contained in a blood transfusion goes into the circulation. Just based on this, we might reduce the amount to 400 mg.. We might knock this value down further by noting there will substantial individual variation. There is a great deal of uncertainty in this estimate.

But the bottom line is that a very high dose will be required. When we consider other problems—that the withdrawal-transfusion paradigm for blood doping would probably not be favored by someone like Froome, who could afford the centrifuge necessary to separate red cells from plasma, then freeze them—this explanation doesn’t look very likely to me. Based on what evidence I’ve seen so far, I think oral dosing is the best explanation. But I look forward to any new information that could affect this conclusion.
Last edited by Merckx index on 16 Dec 2017 02:59, edited 9 times in total.
Merckx index
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Re: All About Salbutamol

16 Dec 2017 01:53

The dehydration claim falls away because the test verifies the urine for dehydration so it’s ng per ml is tested correctly.

Image
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Re: All About Salbutamol

16 Dec 2017 02:01

Red Rick wrote:
thehog wrote:Froome’s hydration GSK testing, its on the low side.

Image

Yeah, the guy is a beast in scorching heat, how would he have dehydration issues at 20 degrees?


What it proves is Froome is not predisposed to hyper-dehydration, he is most normal in this regard.
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Re: All About Salbutamol

16 Dec 2017 02:23

Merckx index wrote:Here’s a summary of the Froome case as I see it.


Seriously impressive piece of work. Thank you! I look forward to seeing it plagiarized without attribution by journalists in the coming days.
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Re: All About Salbutamol

16 Dec 2017 02:27

Merckx index wrote:Here’s a summary of the Froome case as I see it.

[...]

4. The other explanation for his high level is that it was the result of a blood transfusion. He had salbutamol in his circulation—the result of intentional doping with probably oral dosing—when he withdrew blood, and when he then transfused this blood, during the Vuelta, the salbutamol of course went into his system as well, and resulted in exceeding the threshold. This explanation has the advantage of accounting for why Froome exceeded the threshold only once—he transfused before the stage—and of course, blood transfusion is a very well established means of performance enhancement, much better supported than simply using salbutamol. In this scenario, salbutamol would probably be a secondary means of doping, not the main factor, and he wasn't necessarily using it all during the Vuelta, except for inhaling it.

[...]

But the bottom line is that a very high dose will be required. When we consider other problems—that the withdrawal-transfusion paradigm for blood doping would probably not be favored by someone like Froome, who could afford the centrifuge necessary to separate red cells from plasma, then freeze them—this explanation doesn’t look very likely to me. Based on what evidence I’ve seen so far, I think oral dosing is the best explanation. But I look forward to any new information that could affect this conclusion.

I'm not following. Why would using blood bags (something that is overwhelmingly likely) reduce the chance that option number 3 is also the case?

I think his performances on stages 17 & 18 allude to him having used a blood bag between the two stages. So the only thing that separates option 3 and 4 (imo) is whether or not said bag was dirty or not (and if so how much it contributed with), not if the bag alone could cause it.

Regarding the finer details of the operation of blood bags, do we have any knowledge of what the praxis is like that isn't a decade old at this point? I'd guess that the passport means that one concentrated part of the off-season is when all blood is extracted is less likely. And given that it has been alluded to that high altitude training camps are (also) used to masks swings in the passport, I find it more likely that blood is extracted multiple times during the season.
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Re: All About Salbutamol

16 Dec 2017 02:47

Great find, hog. I modified my long post above to include that.

Netserk wrote:I'm not following. Why would using blood bags (something that is overwhelmingly likely) reduce the chance that option number 3 is also the case?


I'm assuming he used salbutamol during training, but avoided it during races when he knew he would be tested. To be sure, it seems he could have beaten the tests, anyway, but it's an extra risk that might not have been worth the benefit.

I think his performances on stages 17 & 18 allude to him having used a blood bag between the two stages. So the only thing that separates option 3 and 4 (imo) is whether or not said bag was dirty or not (and if so how much it contributed with), not if the bag alone could cause it.


The transfusion scenario has been a favorite because it's assumed he couldn't get away with taking large doses of salbutamol throughout a GT. Now it seems that he could have. So yes, you have a point, one could argue that both factors are involved. But I was really addressing the people who think transfusion must be the only explanation, who are deciding between that and oral dosing during the race.

I'm not sure if this is your point, but your post makes me realize that even if a transfusion likely could not be the sole cause of a 2000 ng/ml urine level, it might make some contribution which, added to the oral dosing, would result in the final level. Still, the contribution of the transfusion would be relatively minor. I don't see that it could lift a 1000 ng/ml level to 2000 ng/ml. But it could add to the other factors involving timing that I mentioned.

Regarding the finer details of the operation of blood bags, do we have any knowledge of what the praxis is like that isn't a decade old at this point? I'd guess that the passport means that one concentrated part of the off-season is when all blood is extracted is less likely. And given that it has been alluded to that high altitude training camps are (also) used to masks swings in the passport, I find it more likely that blood is extracted multiple times during the season.


The risky part of withdrawal-transfusion is withdrawal, because the loss of red cells stimulates reticulocytes. Transfusion is less of a problem, because while it reduces retics, this can be counteracted with small doses of EPO. But I don't think there's much of a risk difference in withdrawing, removing red cells, and freezing, vs. withdrawing, storing the whole blood, then withdrawing more and transfusing the stored blood. In either case, you need a withdrawal for every blood bag that you transfuse during a race.
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Re: All About Salbutamol

16 Dec 2017 02:50

Netserk wrote:
Merckx index wrote:Here’s a summary of the Froome case as I see it.

[...]

4. The other explanation for his high level is that it was the result of a blood transfusion. He had salbutamol in his circulation—the result of intentional doping with probably oral dosing—when he withdrew blood, and when he then transfused this blood, during the Vuelta, the salbutamol of course went into his system as well, and resulted in exceeding the threshold. This explanation has the advantage of accounting for why Froome exceeded the threshold only once—he transfused before the stage—and of course, blood transfusion is a very well established means of performance enhancement, much better supported than simply using salbutamol. In this scenario, salbutamol would probably be a secondary means of doping, not the main factor, and he wasn't necessarily using it all during the Vuelta, except for inhaling it.

[...]

But the bottom line is that a very high dose will be required. When we consider other problems—that the withdrawal-transfusion paradigm for blood doping would probably not be favored by someone like Froome, who could afford the centrifuge necessary to separate red cells from plasma, then freeze them—this explanation doesn’t look very likely to me. Based on what evidence I’ve seen so far, I think oral dosing is the best explanation. But I look forward to any new information that could affect this conclusion.

I'm not following. Why would using blood bags (something that is overwhelmingly likely) reduce the chance that option number 3 is also the case?

I think his performances on stages 17 & 18 allude to him having used a blood bag between the two stages. So the only thing that separates option 3 and 4 (imo) is whether or not said bag was dirty or not (and if so how much it contributed with), not if the bag alone could cause it.

Regarding the finer details of the operation of blood bags, do we have any knowledge of what the praxis is like that isn't a decade old at this point? I'd guess that the passport means that one concentrated part of the off-season is when all blood is extracted is less likely. And given that it has been alluded to that high altitude training camps are (also) used to masks swings in the passport, I find it more likely that blood is extracted multiple times during the season.


If he was on a two bag TDF, the only real time to withdraw would be between the Tour and Vuelta. He’d have to recover sufficiently with rest and I would think to maintain weight in that period he was injecting salbutamol. It’s a better drug then say Clen because you have a thereshold to play with and OOC. It looks like the withdrawal of blood didn’t give him enough clearance time. I’d look to his schedule between the Tour and Vuelta.
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16 Dec 2017 02:57

Excellent posts, MI.

What do you think of "By Jove, I forgot I had already taken my salbutamol tablet and I took a second one"? Would that be a good fit for (3) and for all the data we have available at the moment?
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Re: All About Salbutamol

16 Dec 2017 03:05

Merckx index wrote:(Edit: I just started looking at the Sundby CAS case linked upthread. It turns out the athlete took nearly ten times the amount of allowed salbutamol, via a nebulizer. So hardly surprising that he exceeded the threshold. His argument apparently is that it was medically necessary, and that since it was administered orally, would not have been performance-enhancing. I also bring this up because it further supports my point, below, that it's possible to take a much larger than allowed dose and not exceed the threshold. This athlete's urine level was actually lower than Froome's, despite taking 15 mg of salbutamol in a period of just a few hours.)


In the Sundby case, he did a pharmacokinetic study (London Study) taking 5mg nebulised and hit an astronomic 4800 ng/mL. He then did a second study at WADA (Oslo Study) taking 1.6mg through an inhaler and again blew the decision limit with a measurement of 1700 ng/mL. And as I've said before, trying to linearly extrapolate from urine level to doses taken is nonsensical. The only scientifically tested classification is over/under therapeutic limit as per WADA, no ones testing linear fit for populations (good choice, the data is all over the place).

Also, the reason they don't adjust for specific gravity is because they claim to have designed the limit with SG taken into account. This is discussed in the Petacchi CAS decision (this was Petacchis argument after all).

I would also note that, beyond the whole "do. not. extrapolate. to. doses." thing, taking 4-8mg of salbutamol through an inhaler would be quite the experience that sees you lose your breakfast.

(Also, you realize you can take all the salbutamol in the world with a TUE, right? If he wanted to take excessive doses for performance gain all through the race, he would simply get a TUE. Much less headache than this right now.)
Last edited by hazaran on 16 Dec 2017 03:38, edited 2 times in total.
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Re: All About Salbutamol

16 Dec 2017 03:20

Merckx index wrote:I'm not sure if this is your point, but your post makes me realize that even if a transfusion likely could not be the sole cause of a 2000 ng/ml urine level, it might make some contribution which, added to the oral dosing, would result in the final level. Still, the contribution of the transfusion would be relatively minor.


Ya, this seems quite important, but it depends on all the math. I really appreciate you putting effort into that, certainly nowhere near my skill set.

Couple of other factors I've wondered about, based on my long time lurking in the clinic here :) I thought there was a suggestion that transfusions don't take immediately. Like, maybe part of the reason for the bad day after a rest day thing is settling in to the effects of the transfusion? Similarly, I thought that was part of the potential explanation for Floyd, back in the day. Bad reaction to the transfusion, so boost the testosterone to improve it a bit, or something like that. The other thought is, do we know for sure they tested for salbutamol every day? I thought they sometimes don't test for some things? Admittedly that might be 10 year old methodology (or flawed recollection, whatever), and nowadays they might throw the book at every sample?
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Re: All About Salbutamol

16 Dec 2017 03:49

hazaran wrote:
In the Sundby case, he did a pharmacokinetic study (London Study) taking 5mg nebulised and hit an astronomic 4800 ng/mL.


In the nebulizer study, the 4800 ng/ml was reported after the third of three 5 mg doses. The level was a little over 3000 ng/ml following the first dose. This is a little different from the rough relationship I suggested for oral doses, but is consistent with the fact that inhaled drug should get into the circulation and hence urine faster and in greater quantities than that taken orally. And as I have emphasized all along, there is substantial individual variability.

He then did a second study at WADA (Oslo Study) taking 1.6mg through an inhaler and again blew the decision limit with a measurement of 1700 ng/mL. And as I've said before, trying to linearly extrapolate from urine level to doses taken is nonsensical. The only scientifically tested classification is over/under therapeutic limit as per WADA, no ones testing linear fit for populations (good choice, the data is all over the place).


From the CAS document:

the specific gravity adjusted maximum concentration of approximately 1480 ng/ml occurred at about four hours after the start of the study and approximately 3.5 hours after the administration of the last dose. The largest unadjusted concentration measured was approximately 1700 ng/ml


From this passage, one can conclude that the entire dose was given within thirty minutes, so like the study I discussed in which bolus doses were used, it doesn't qualify as permitted under WADA standards, which allow only 800 ug in a twelve hour period. The instructions to Sundby were to demonstrate that “the test results of the Samples were the consequence of the use of the therapeutic inhaled dose up to the maximum of 1,600 μg/24h of salbutamol”. It doesn’t say that the dose has to be administered over that entire period, only within that period. So administering it within 30 minutes qualifies, even though it does not satisfy the WADA requirement (which rule may not even have been in effect at that time, I don’t know; but it is now).

Furthermore, note the immediately following passage from an amendment:

1600 μg of Salbutamol was delivered from an MDI with spacer during 28 minutes and Urinary salbutamol excretion levels were repeatedly measured up to 7 hours after dose delivery. At two occasions, salbutamol levels in urine exceeded the levels measured during competition 1703 ng/ml and 1631 ng/ml compared to 1340 ng/ml and 1360 ng/ml. I believe this data strongly support the statement that Sundby did not inhale salbutamol exceeding recommended maximum dose of 1600μg


You can see from this passage that Sundby is simply trying to establish that 1600 ug given in some time period can result in levels above the threshold. I don't have any problems with these results. They aren't inconsistent with the points I have made.

Also, the reason they don't adjust for specific gravity is because they claim to have designed the limit with SG taken into account. This is discussed in the Petacchi CAS decision (this was Petacchis argument after all).


Thanks for that information.

I would also note that, beyond the whole "do. not. extrapolate. to. doses." thing, taking 4-8mg of salbutamol through an inhaler would be quite the experience that sees you lose your breakfast.


Which is why I have been talking about oral doses.

(Also, you realize you can take all the salbutamol in the world with a TUE, right? If he wanted to take excessive doses for performance gain all through the race, he would simply get a TUE. Much less headache than this right now.)


Surely it can't be that simple? Why wouldn't lots of riders get a TUE so they could do this? I don't know, but I'm guessing that taking more than 1600 ug in 24 hours is unusual, and it might be hard to convince a doctor that you need more if in fact you really don't. But this is a good point for further discussion.
Last edited by Merckx index on 16 Dec 2017 04:05, edited 3 times in total.
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16 Dec 2017 03:59

The question of if, when and how many leaks Froome took during the stage should be solvable. A) there were a lot of other riders in the race and the red jersey is tracked by quite a few; b) I thought I saw that there was full stage video available, so it could be viewed to track red jersey piss breaks.

The salbutamol concentration discussion by MI raises interesting questions about why Froome took late in stage pass breaks in other races.
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Re: All About Salbutamol

16 Dec 2017 04:10

Merckx index wrote:Surely it can't be that simple? Why wouldn't lots of riders get a TUE so they could do this? I don't know, but I'm guessing that taking more than 1600 ug in 24 hours is unusual, and it might be hard to convince a doctor that you need more if in fact you really don't. But this is a good point for further discussion


The Sundby decision makes extensive references to TUEs, among others

"As a result, in the WADA’s opinion, a TUE would be necessary for the use of salbutamol with a nebulizer, in the same way as a TUE is necessary for the administration of an amount larger than 1,600 μg per day."

Sundby had two tests over the limit and even mentions how he would have obtained a TUE after the first one had they informed him in a timely manner (which they didn't, in clear breach, but CAS don't give a ****)

So I figured it is still possible with a TUE to take as much as you want (well, whatever the good doctor puts into the TUE you are taking, but I guess if you have one they just won't test your urine). Makes you wonder why they didn't do that when they decided to increase the dose per Froomes story. Asking to take more of your asthma drug after your asthma worsened seems pedestrian given the TUE stuff we have seen.
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Re: All About Salbutamol

16 Dec 2017 06:52

Merckx index wrote:
Also, someone help me out here. Are nature breaks common in GT stages? I know they happen sometimes, but would a rider usually stop at some point? Because with a relatively rapidly cleared drug like salbutamol, whether or not you stopped to piss before the end of the stage could be critical.


Yes.
Image
It would be mandatory to at least allow for the possibility. Also, Froome would effectively get to dictate when to have his own urination break, if that were necessary in addition to 'pre-scheduled' breaks. It would be unacceptable to attack the GT leaders while they were on a break to urinate. TV coverage of the stage would not prove anything either way, because of the different possible 'unscheduled' methods (on or off the bike)

And while on this general subject, I asked earlier what evidence there was that Froome used salbutamol previously. All I got in response was that he used an inhaler in 2014. But that's after the great transformation! What about before? Again, this seems to me fairly critical.


Anecdotal report, without elaboration, that Sky claimed in 2014 Froome has used asthma inhalers consistently since he was a teenager. Requires some more investigation, of the source and evidence, for this claim by Sky.
Much was made of the 'bilharzia' but asthma was never mentioned prior to 2014
ClassicomanoLuigi
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Re: All About Salbutamol

16 Dec 2017 08:35

I finally found the document explaining the requirements for a TUE for salbutamol:

Medical History
• Clinical Examination
• Spirometry report, or
• Bronchial Provocation Test
• Treating Physician contact info.
• Explanation as to why salbutamol, salmeterol or formoterol are not appropriate


There are some more specific requirements listed at the site, e.g., certain minimum changes in the amount of air you can exhale under certain conditions. My guess is that it would be hard to get a doctor to sign off on these if they weren’t really the case. Riders may decide that’s too much trouble, and that if they’re careful, they can take as much as they need without reaching the threshold.

https://www.wada-ama.org/sites/default/files/resources/files/11-_mountjoy_margo_-_paris_2014_-medical_issues_asthma.pdf

An interesting remark from Petacchi, while commenting on Froome:
“When I went to UCI after they contacted me, they showed me the history of all of my controls. All the controls were different, not one the same. It depends how soon you used it before the control, how concentrated your urine was.

“I used it more or less the same every time, but it’d vary: 300, 400, or 700 or 500. That time it was 1200, but that was the only one where I concentrated urine.

http://www.cyclingweekly.com/news/racing/former-pro-alessandro-petacchi-disbelief-chris-froome-salbutamol-levels-363098#ZDlcA3FpzYDTIbio.99

Yes, the results will vary depending on the time between taking the substance and furnishing a urine sample, but I have been referring all along to studies set up so that peak urine levels are obtained. For Petacchi to have levels of 500 or more ng/ml., via inhaling, he probably would have had to inhale the 1600 ug maximum, though at that time I don’t think they had that limit. In fact, I’m a little confused, because WADA switched to to the threshold, not requiring a TUE, in 2010, after Pettachi’s case, yet his positive clearly resulted from exceeding that threshold. In any case, he was probably using higher oral doses, and was careful to urinate before the end of the stage. The one time he got popped, maybe he couldn’t. From the many studies reporting a significant effect of salbutamol on short term anaerobic power, it’s obvious that he would be the ideal candidate to benefit from the drug. I tried to pull up his CAS decision, but it won’t open in my computer.

Ulissi I think did not appeal to CAS. His national (Swiss) committee recommended the ban, which he accepted, and I think UCI did not appeal it. His lawyer argued that his urine levels jumped because of a crash, LOL.
Merckx index
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16 Dec 2017 10:08

"Discrimination of Prohibited Oral Use of Salbutamol from Authorized Inhaled Asthma Treatment"

http://clinchem.aaccjnls.org/content/46/9/1365

The metabolism of salbutamol is stereoselective, so to know the ratio of S/R enantiomers of salbutamol reveals a lot about how the dose was administered. That would be one good forensic approach
ClassicomanoLuigi
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16 Dec 2017 11:07

This is good stuff people
Veni, Vidi, Kirby

I came, I saw, I was dead wrong as per usual
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