All About Salbutamol

[Clyde Puffer]

Re:

Does anyone know at what levels cardiac arrest becomes a real possibility with Salbutomol? Obviously there's a risk. Just thinking out loud, that with a reading of 2000ng/ml after the stage, a 4 hour half life, Froome was closer to a 4000ng/ml reading at the start line from transfusing 1 litre of blood, if that is what he did?

So, if 1 litre of transfused blood can raise salbutomol levels in urine to 4000ng/ml at start of a stage when obviously that's got diluted with your other 5 litres already in your body, does that mean he had the equivalent of 4000ng/ml x (5 litres) in his body at the time of withdrawing his blood. i.e. he would have had a urine reading of something like 20,000ng/ml had he tested his urine when withdrawing his blood initially or does it not work like that once processed from the blood to the urine in the body?

Q .Does anyone know at what levels cardiac arrest become a possibility?"
A. The LD50 for oral salbutamol is 660mg/kg body weight This is the amount of Sal. that would kill 50 percent of a population of rats which have a similar physiology to humans If you scale this up for a 70kg human you would have a lethal,dose of 70x660=46200mg.
So there you have it 42.6 grams, or 462000 puffs of inhaler

PS this is just the lethal dose, a cardiac arrest could occur sooner

 

[Merckx index]

We've discussed many of the questions being raised recently earlier in the thread. To repeat, transfusion is not a possible source of the salbutamol. The doses needed would be far too high, probably more than 10x that 24 mg per day cited for body builders.

The 2000 ng/ml level is attainable with an 8 mg oral dose according to one study I posted upthread. Sam's point about the level's probably being even higher at some point is possible, but Froome's time to the end of the stage was about 4:20, so if he had taken a large oral dose at the start, he would have a high urine level unless he urinated at some point along the way. That's a key factor we don't know about, though Froome said he has records of that on every stage. In any case, though, Froome's urinary level is consistent with an oral dose that is well within the range reported by body builders and others. It's not so small that one would consider it micro-dosing, nor so large that it would be unprecedented, particularly when you consider the possible development of tolerance.

Also to repeat, Sundby took 15 mg by nebulizer in a few hours, and had a maximum urinary level of > 4000 ng/ml. It was about 3000 after the first 5 mg dose. He apparently had no adverse effects.

With regard to metabolic effects, I posted upthread a recent (2014) review of b-adrenergic agonists. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2439523/#bib32

I didn't see anything there that jumps out as indicating salbutamol might be used as a masking agent, but certainly there are potential PE effects, particularly increasing blood flow to the heart. The author cites several studies of performance enhancement, which I believe have been linked upthread. In one of them, a single oral dose increased endurance as determined by time to exhaustion. Clearly the effects may be very different on different subjects, which may contribute to the difficulty of establishing PE effects in lab studies, but that doesn't mean some individuals couldn't have a major benefit. Salbutamol is structurally somewhat similar to clenbuterol, but is short acting,whereas the latter has a half life of about ten times greater. Another thing to keep in mind is that it's a partial agonist, which means it can act as an antagonist and actually block the effects of agonists under some circumstances.

As an aside, the authors make a very interesting insight into the value of salbutamol for swimmers. I was quite surprised by Dickinson's claim that 70% of British swimmers have EIA. The authors point out that the time over which you can hold your breath underwater can be critical in a race (particularly short ones), due to the fact that swimmers can move faster underwater than on the surface. Hence, long dives at the start and long push offs on turns. Apparently as a result of this, there have been rule changes governing when the salbutamol can be inhaled.

 

[sittingbison]

Samhocking You've missed the point with the photo...(with a wide lens) sure Martin's arms are skeletal like all cyclists these days, but Dawgs right arm is an exhibit from the Freak Circus.

Thanks for the round up MI. I still think there are several contributing factors that led to Dawg being under 1000 on Stages 17 and 19, but 2000 on his magical recovery of Stage 18. Obviously something went wrong. A blood bag full to the brim with OOC Sal might not get him there, nor do a couple of puffs before during and after the race. Nor does a tablet. Combined they might, especially if he took an overdose of tablets...handed two instead of one in the cocktail, a label misread, given a Sal tablet instead of a headache tablet like champion Aussie swimmer Samantha Riley a decade ago etc

 

[bigcog]

Re:

Samhocking You've missed the point with the photo...(with a wide lens) sure Martin's arms are skeletal like all cyclists these days, but Dawgs right arm is an exhibit from the Freak Circus.

Thanks for the round up MI. I still think there are several contributing factors that led to Dawg being under 1000 on Stages 17 and 19, but 2000 on his magical recovery of Stage 18. Obviously something went wrong. A blood bag full to the brim with OOC Sal might not get him there, nor do a couple of puffs before during and after the race. Nor does a tablet. Combined they might, especially if he took an overdose of tablets...handed two instead of one in the cocktail, a label misread, given a Sal tablet instead of a headache tablet like that Aussie swimmer a decade ago etc

I am not sure why there is this fixation on a blood bag. MI has shown/stated given the dilution factor involved it wouldn't be a factor as has another doctor:

"Former pro Joerg Jaksche suggested that if somebody used a blood bag, and had been using an inhaler at the time when the blood was taken out, that this could be carried over. Is this suggestion unfounded?

I think that would be very, very unlikely. That would be within the grounds of science fiction, rather than a real scenario.

You would have to have an absolutely massive dose of Ventolin the day he gave the blood. And then it would have to stay stable and not degrade over the period of time that it was being kept. It is off the wall, that, I think."

https://cyclingtips.com/2017/12/certainly-doesnt-look-good-doctor-speaks-froome-case/

 

[Netserk]

It is because the positive is from his comeback day. So a blood bag is likely to have been used. Now, while a contaminated bag might not change much, is it farfetched to think that there might be some cocktail involved which includes Sal? Sure the bag theory might be a big red herring, but it is highly plausible that a bag was used and it does go a long way to explain why the positive was on that particular day.

 

[thehog]

Re: Re:

Samhocking You've missed the point with the photo...(with a wide lens) sure Martin's arms are skeletal like all cyclists these days, but Dawgs right arm is an exhibit from the Freak Circus.

Thanks for the round up MI. I still think there are several contributing factors that led to Dawg being under 1000 on Stages 17 and 19, but 2000 on his magical recovery of Stage 18. Obviously something went wrong. A blood bag full to the brim with OOC Sal might not get him there, nor do a couple of puffs before during and after the race. Nor does a tablet. Combined they might, especially if he took an overdose of tablets...handed two instead of one in the cocktail, a label misread, given a Sal tablet instead of a headache tablet like that Aussie swimmer a decade ago etc

I am not sure why there is this fixation on a blood bag. MI has shown/stated given the dilution factor involved it wouldn't be a factor as has another doctor:

"Former pro Joerg Jaksche suggested that if somebody used a blood bag, and had been using an inhaler at the time when the blood was taken out, that this could be carried over. Is this suggestion unfounded?

I think that would be very, very unlikely. That would be within the grounds of science fiction, rather than a real scenario.

You would have to have an absolutely massive dose of Ventolin the day he gave the blood. And then it would have to stay stable and not degrade over the period of time that it was being kept. It is off the wall, that, I think."

https://cyclingtips.com/2017/12/certainly-doesnt-look-good-doctor-speaks-froome-case/

The problem with asking regular Doctors about how and why athletes use their medicines is pointless. They have no practical understanding on how doping works. There are also no studies on the methods used by cyclists and just how beneficial each drug is in terms of performance. Dr. Ferrari & Dr. Leinders know more than the journalists keep interviewing on the subject but clearly they don’t give interviews.

We had the same set of Doctors during the Wiggins affairs telling us that Kenalog wasn’t performance enhancing when several former dopers came forward speaking to its benefits.

 

[lefourbe]

Re: Re:

Also if it's not a transfusion, what's the most likely explanation for the 2000 mg?

-Inhaling not an option as that would be an insane amount of puffs.
-Injecting/oral: ok but then it can only be an accidental surdose or mix up with other pills as CF/SKY knew they would be tested. Also is there really an PE effect for just one dose, one day?
- Combination of the above?
- Nebulizer. Apparently no more PE effect than Inhaler?

Samhocking You've missed the point with the photo...(with a wide lens) sure Martin's arms are skeletal like all cyclists these days, but Dawgs right arm is an exhibit from the Freak Circus.

Thanks for the round up MI. I still think there are several contributing factors that led to Dawg being under 1000 on Stages 17 and 19, but 2000 on his magical recovery of Stage 18. Obviously something went wrong. A blood bag full to the brim with OOC Sal might not get him there, nor do a couple of puffs before during and after the race. Nor does a tablet. Combined they might, especially if he took an overdose of tablets...handed two instead of one in the cocktail, a label misread, given a Sal tablet instead of a headache tablet like that Aussie swimmer a decade ago etc

I am not sure why there is this fixation on a blood bag. MI has shown/stated given the dilution factor involved it wouldn't be a factor as has another doctor:

"Former pro Joerg Jaksche suggested that if somebody used a blood bag, and had been using an inhaler at the time when the blood was taken out, that this could be carried over. Is this suggestion unfounded?

I think that would be very, very unlikely. That would be within the grounds of science fiction, rather than a real scenario.

You would have to have an absolutely massive dose of Ventolin the day he gave the blood. And then it would have to stay stable and not degrade over the period of time that it was being kept. It is off the wall, that, I think."

https://cyclingtips.com/2017/12/certainly-doesnt-look-good-doctor-speaks-froome-case/

The problem with asking regular Doctors about how and why athletes use their medicines is pointless. They have no practical understanding on how doping works. There are also no studies on the methods used by cyclists and just how beneficial each drug is in terms of performance. Dr. Ferrari & Dr. Leinders know more than the journalists keep interviewing on the subject but clearly they don’t give interviews.

We had the same set of Doctors during the Wiggins affairs telling us that Kenalog wasn’t performance enhancing when several former dopers came forward speaking to its benefits.

 

[Merckx index]

Re: Re:

The problem with asking regular Doctors about how and why athletes use their medicines is pointless. They have no practical understanding on how doping works. There are also no studies on the methods used by cyclists and just how beneficial each drug is in terms of performance. Dr. Ferrari & Dr. Leinders know more than the journalists keep interviewing on the subject but clearly they don’t give interviews.

We had the same set of Doctors during the Wiggins affairs telling us that Kenalog wasn’t performance enhancing when several former dopers came forward speaking to its benefits.

This point is fine with respect to performance enhancement, but it’s irrelevant to the transfusion scenario. We’re not discussing whether transfusion is performance enhancing, we’re discussing whether there could be enough drug in the blood to result in Froome’s urinary level following transfusion. Answering this doesn’t depend on any hidden knowledge; it’s a relatively simple mathematical problem. To be sure, it’s very difficult to make an estimate with much precision, but the amounts involved are so enormous that precision is unnecessary.

As another perspective, as you yourself have pointed out, Froome’s urine level of salbutamol was about 50-100,000 times higher than Contador’s CB level. Granted, the large difference in rates of clearance from the blood impacts urine levels, but it still indicates the enormous difference in amount of drug that Froome would have to ingest vs. Contador.

I’m of course very much aware of how convenient the transfusion scenario would be; when you have a one day spike in some substance, clearly standing out from levels measured the days before or after, transfusion seems like the obvious explanation. But it just doesn’t work. The only way it could work is if someone spiked Froome’s hypothetical blood bag with salbutamol. I guess that’s not impossible, but if the choice is between that and oral dosing during the Vuelta to get some PE effect, I know which way I’m going. As Sherlock Holmes used to say, when you have eliminated all the probable causes, whatever remains, no matter how improbable, has to be the answer.

I agree that those two articles from South Bay that have been linked here are really quite powerful, making a lot of important points. But the author only cites one article, an overview of salbutamol on a body-building site. This article in turn cites four references in support of the claim that salbutamol is performance enhancing. The first reference in this overview is a study of lab rats, and doesn’t actually involve salbutamol, but other b2-agonists like clenbuterol. The next two studies, both by the same group, report an increase in muscle strength, but apparently these increases were relatively modest, as the significance was reported at the < 0.05 level. The fourth study, which has been mentioned here before, reported an increase in endurance in a cycling ergometer. This is very intriguing, of course, but it does have to be emphasized that other researchers haven’t found such effects. I believe most of the reproducible effects have been on anaerobic power.

Given that the best established effects of salbutamol are on weight loss and building lean muscle mass, it doesn’t really explain why Froome would take it during the Vuelta. As haz and others here have pointed out, by stage 18 he had completed nearly two GTs in about two months, so weight loss would not have been a problem. If salbutamol has anabolic, or muscle building properties, then it could be a recovery aid, but I don’t believe this has been documented very thoroughly. The studies cited at the body building site examined its effects over several months. This would make it appropriate for training during the offseason, but I’m not clear whether it would help day-to-day recovery during a GT.

All that said, this is one situation where it isn’t all about the documented properties of a substance; it’s also about the perception of its properties. Body builders use it because they think it helps them. Cyclists may feel the same way. That’s all that actually matters when discussing the probability that a substance was used.

While I’m at it, a couple of minor errors in the articles:

But cyclists also maintain muscle mass by using a class of drugs known as β-agonist receptors.

What he means is drugs that act at b-adrenergic receptors, i.e., b-adrenergic agonists, and more specifically, b2-adrenergic agonists.

What was most interesting about the Petacchi case is that the Barcelona lab which retested his sample concluded that the Salbutamol had not been inhaled.

What they concluded was that while the salbutamol had been ingested with an inhaler, some of the drug was swallowed rather than inhaled, something that’s known to happen. Of course, the author’s point still stands, this is a joke of a decision, but this is how CAS rationalized it without actually contradicting themselves. Officially, the positive was due to accidental inhalation of more than the allowable dose, some of which was swallowed.

Finally, I thought about this theory that UCI leaked the Froome AAF, and that this could be used by Froome to argue that his rights weren’t protected, when someone had this great line on CNN, in regard to the Trump investigation:

If you have the law on your side, argue the law
If you don’t have the law on your side, argue the facts
If you don’t have the facts on your side, create a distraction.

 

[thehog]

Sporting arbitration has none of the protection of the courts in terms of due process not being followed or not, none whatsoever. Even chain of custody issues have little to no bearing. And for all we know it was Sky who leaked the story and not the CADF. It has no bearing on Froome’s situation. It should also be noted that Froome’s behaviour before the leak was of a man who knew this was going away. Froome will be hard pressed to suggest he rights have been infringed in any way.

My comments with regards to the statements of regular Doctors was not to suggest that the containination came from a transfusion, it’s that they have zero experience with no doping and have no idea about the absurd lengths some cyclists go to for performance enhancement. No doctor knows you should mix your androgel with olive oil or sprinkle washing power over your urine sample to fuzzy the EPO test. Your time is better spent on a bodybuilding forum where they talk openly about gains or no gains or the dark web!

 

[samhocking]

We've discussed many of the questions being raised recently earlier in the thread. To repeat, transfusion is not a possible source of the salbutamol. The doses needed would be far too high, probably more than 10x that 24 mg per day cited for body builders.

The 2000 ng/ml level is attainable with an 8 mg oral dose according to one study I posted upthread. Sam's point about the level's probably being even higher at some point is possible, but Froome's time to the end of the stage was about 4:20, so if he had taken a large oral dose at the start, he would have a high urine level unless he urinated at some point along the way. That's a key factor we don't know about, though Froome said he has records of that on every stage. In any case, though, Froome's urinary level is consistent with an oral dose that is well within the range reported by body builders and others. It's not so small that one would consider it micro-dosing, nor so large that it would be unprecedented, particularly when you consider the possible development of tolerance.

Also to repeat, Sundby took 15 mg by nebulizer in a few hours, and had a maximum urinary level of > 4000 ng/ml. It was about 3000 after the first 5 mg dose. He apparently had no adverse effects.

With regard to metabolic effects, I posted upthread a recent (2014) review of b-adrenergic agonists. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2439523/#bib32

I didn't see anything there that jumps out as indicating salbutamol might be used as a masking agent, but certainly there are potential PE effects, particularly increasing blood flow to the heart. The author cites several studies of performance enhancement, which I believe have been linked upthread. In one of them, a single oral dose increased endurance as determined by time to exhaustion. Clearly the effects may be very different on different subjects, which may contribute to the difficulty of establishing PE effects in lab studies, but that doesn't mean some individuals couldn't have a major benefit. Salbutamol is structurally somewhat similar to clenbuterol, but is short acting,whereas the latter has a half life of about ten times greater. Another thing to keep in mind is that it's a partial agonist, which means it can act as an antagonist and actually block the effects of agonists under some circumstances.

As an aside, the authors make a very interesting insight into the value of salbutamol for swimmers. I was quite surprised by Dickinson's claim that 70% of British swimmers have EIA. The authors point out that the time over which you can hold your breath underwater can be critical in a race (particularly short ones), due to the fact that swimmers can move faster underwater than on the surface. Hence, long dives at the start and long push offs on turns. Apparently as a result of this, there have been rule changes governing when the salbutamol can be inhaled.

Thanks for the explanation MI. I was thinking of the levels being so high at start of stage/night before from a transfusion, that he would be close to him having cardiac problems, but is sounds like the dose is relatively within range to still function normally.

It seems the circumstances are pointing towards salbutomol not being a mistake from a transfusion while loosing weight like we assume it's' normally used for, but being used to enhance performance in some way we don't know about during the race then?

Salbutomol's elimination half-life in the urine is 2.7 - 5.5 hours. Stage 18 was only 4 hours long. If we say he took it orally in the morning another 4 hours before the stage, his half-life window would be around 8 hours meaning the 2000 reading after the stage would actually only have needed that other 4 hours to drop to around the 1000 mark and so in the clear.
If I was betting on what I think now, I would say his oral dosage is him doing this privately, but real asthma hit him, team doctor administered a higher dose than normal, knowing there's a fairly big cushion before getting anywhere near the 1000 mark, Froome couldn't exactly say, sorry i've been self administering oral (not allowed) salbutomol without telling you and what the doctor gave him, was just enough on a short stage to trip anti-doping. End of the day had he taken the pill 2 hours earlier and the stage be 2 hours longer his reading would be around the 1000 level including what the Team doctors increased dose.

 

[Wiggo's Package]

Re: Re:

Finally, I thought about this theory that UCI leaked the Froome AAF, and that this could be used by Froome to argue that his rights weren’t protected, when someone had this great line on CNN, in regard to the Trump investigation:

If you have the law on your side, argue the law
If you don’t have the law on your side, argue the facts
If you don’t have the facts on your side, create a distraction.

That's a great quote

Of course Trump may go nuclear - sack Mueller and give immunity to his team

Dawg must be gutted that Brian lost the UCI election at such a critical moment

 

[hazaran]

Re: Re:

Finally, I thought about this theory that UCI leaked the Froome AAF, and that this could be used by Froome to argue that his rights weren’t protected, when someone had this great line on CNN, in regard to the Trump investigation:

If you have the law on your side, argue the law
If you don’t have the law on your side, argue the facts
If you don’t have the facts on your side, create a distraction.

The CAS is all about law, and "leaks" are procedural missteps that they do not look kindly on. It's a point I wanted to make earlier regarding all the kerfuffle about CAS writing it was accidental ingestion or whatever. They still banned him 9 months! Lots of the writing in CAS decisions is just to show they considered the input you gave, because failure on their part to do so is a big procedural no-go. It ultimately doesn't matter much though.

Look at the Contador CAS decision for a case-study. Pages upon pages of minute discussions on clenbuterol, steaks, supplements and what not. But none of that can help you for the prohibited substance violation, it's strict liability! So lots of the writing is just to sway them for the parts where they have leeway, like slightly reducing the ban you get.

 

[thehog]

Re: Re:

Finally, I thought about this theory that UCI leaked the Froome AAF, and that this could be used by Froome to argue that his rights weren’t protected, when someone had this great line on CNN, in regard to the Trump investigation:

If you have the law on your side, argue the law
If you don’t have the law on your side, argue the facts
If you don’t have the facts on your side, create a distraction.

The CAS is all about law, and "leaks" are procedural missteps that they do not look kindly on. It's a point I wanted to make earlier regarding all the kerfuffle about CAS writing it was accidental ingestion or whatever. They still banned him 9 months! Lots of the writing in CAS decisions is just to show they considered the input you gave, because failure on their part to do so is a big procedural no-go. It ultimately doesn't matter much though.

Look at the Contador CAS decision for a case-study. Pages upon pages of minute discussions on clenbuterol, steaks, supplements and what not. But none of that can help you for the prohibited substance violation, it's strict liability! So lots of the writing is just to sway them for the parts where they have leeway, like slightly reducing the ban you get.

Exactly. Look at the Landis case, pages upon pages of changing and conflicting testimony but none of it had any bearing on the outcome.

Steven Colvert case for EPO is another example, most likely he didn’t even test positive but hat is too bad. Suspended for two years years.

 

[Djoop]

Deleted post

 

[Angliru]

Obviously, a high dose of Salbutamol indicates severe breathing problems. We can all see the footage, and the end result compared to a peloton of athletes in their prime. Used to enhance his performance, and probably miscalculated the max -possibly because of a blood transfusion. I'm eager to find out, but it doesn't matter all that much. He had an unfair advantage, that's what counts.

I don't know when Sky left the mpcc exactly, but it's only the fourth scandal since. You had the rider who came forward about painkiller abuse within the team, the mysterious medical package delivery,TUEs during TDF wins, and now this. Add UCI's reluctance to do their job properly when it involves 35 million, and basicly nothings changed since the US Postal scam.

Were they ever part of the MPCC?

 

[bigcog]

Obviously, a high dose of Salbutamol indicates severe breathing problems. We can all see the footage, and the end result compared to a peloton of athletes in their prime. Used to enhance his performance, and probably miscalculated the max -possibly because of a blood transfusion. I'm eager to find out, but it doesn't matter all that much. He had an unfair advantage, that's what counts.

I don't know when Sky left the mpcc exactly, but it's only the fourth scandal since. You had the rider who came forward about painkiller abuse within the team, the mysterious medical package delivery,TUEs during TDF wins, and now this. Add UCI's reluctance to do their job properly when it involves 35 million, and basicly nothings changed since the US Postal scam.

Were they ever part of the MPCC?

No.

 

[Djoop]

Deleted post

 

[Wiggo's Package]

Obviously, a high dose of Salbutamol indicates severe breathing problems. We can all see the footage, and the end result compared to a peloton of athletes in their prime. Used to enhance his performance, and probably miscalculated the max -possibly because of a blood transfusion. I'm eager to find out, but it doesn't matter all that much. He had an unfair advantage, that's what counts.

I don't know when Sky left the mpcc exactly, but it's only the fourth scandal since. You had the rider who came forward about painkiller abuse within the team, the mysterious medical package delivery,TUEs during TDF wins, and now this. Add UCI's reluctance to do their job properly when it involves 35 million, and basicly nothings changed since the US Postal scam.

Were they ever part of the MPCC?

No.

My bad,they rejected to join because ofits medical rules.

IIRC Sky were non-specific about why they wouldn't join MPCC

The reasons are obvious enough now of course

 

[70kmph]

Froomy mathematics

Number of hours racing(4:09:39) +0:10:08 +0:50:00 (interview)
Size of dosage 3 puffs post race
Urine stop ?
Controls = 2000 ng/ml

 

[Djoop]

Deleted post

 

[Merckx index]

Thanks for the explanation MI. I was thinking of the levels being so high at start of stage/night before from a transfusion, that he would be close to him having cardiac problems, but is sounds like the dose is relatively within range to still function normally.

I believe it’s within the range for many people to function more or less normally. Individuals differ, of course.

It seems the circumstances are pointing towards salbutomol not being a mistake from a transfusion while loosing weight like we assume it's' normally used for, but being used to enhance performance in some way we don't know about during the race then?

Probably used for recovery. That seems to be the best guess.

Salbutomol's elimination half-life in the urine is 2.7 - 5.5 hours. Stage 18 was only 4 hours long. If we say he took it orally in the morning another 4 hours before the stage, his half-life window would be around 8 hours meaning the 2000 reading after the stage would actually only have needed that other 4 hours to drop to around the 1000 mark and so in the clear.

The half-life depends on how it’s taken. It’s excreted faster following inhalation, about 2.5 hour half-life from what I’ve heard. More like four hours, more or less, following an oral dose. And these are averages, of course. Individuals may have significantly shorter or longer values.

If I was betting on what I think now, I would say his oral dosage is him doing this privately, but real asthma hit him, team doctor administered a higher dose than normal, knowing there's a fairly big cushion before getting anywhere near the 1000 mark, Froome couldn't exactly say, sorry i've been self administering oral (not allowed) salbutomol without telling you and what the doctor gave him, was just enough on a short stage to trip anti-doping. End of the day had he taken the pill 2 hours earlier and the stage be 2 hours longer his reading would be around the 1000 level including what the Team doctors increased dose.

That scenario, more or less, has occurred to me, but someone as familiar with salbutamol as Froome must be (even if he’s only been taking it for a few years, as I suspect may be the case, that’s still enough time to understand the relationship between dose and urine levels very well) shouldn’t be tripped up in this manner. If he’s been dosing orally successfully, he’s learned to take doses that allow at least some puffs on the inhaler. A few extra puffs, particularly if taken at the end of the stage, soon before testing, might add a few hundred ng/ml to his urine level, but the total should still be nowhere near 2000. Even if, hypothetically, he had been oral dosing and not taking any puffs at all, and started inhaling for the very first time on this stage, and took the entire allowed dose of 800 ug after finishing the stage—that still would likely not be enough to get him to 2000 if his oral dosing alone kept him below 1000. I think something else must be going on.

What? As I’ve emphasized before, if and when he urinates on a stage could be critical. Urine concentrations peak at one hour following inhalation. The kinetics following oral doses are a little slower, and I’ve been unable to access a study that provides them, but let’s make an estimate, using your eight hour period and a half life of four hours. Let’s assume that after four hours, his urine level is 2000 ng/ml, and he urinated then. After another four hours, his level might be approximately 1000 ng/ml.

Now suppose he didn’t urinate after four hours, but only after eight hours. His salbutamol level would be about 1500 ng/ml, the mean of the two levels assuming constant urine flow. So by not relieving himself, he’s increased his urine level by about 50%, or 500 ng/ml. Moreover, the effect can be even greater if he urinates sooner. E.g., suppose he orally dosed at the start of the stage. If he didn’t stop during the stage, his level in this example would be 2000 ng/ml. If he stopped after two hours, his level at that point might be roughly 3000 ng./ml, and if then urinated again, at the end of the stage, it would be about 1000 ng/ml. So now he’s actually doubled his level, from the threshold to the value that has been reported, just by not stopping along the way.

This is a very rough estimate, I really need to see actual data, but it gives you an idea of how much of an effect not urinating before the end of the stage can have. Other factors, like taking extra puffs, particularly after the stage is over, will further contribute, but the real game changer is whether he stops to pee.

The main problem I have with this explanation is that it’s hard to believe he wouldn’t be aware of this. If he didn’t stop to urinate on this stage, it’s probably happened before, and even if in the past when this happened he had a cushion, so to speak, and didn’t exceed the threshold, I would think it would have taught him not to push the envelope—to take doses that will not trigger the threshold even if he can’t stop to urinate. It would obviously be very foolish to plan the dose based on an event you can't guarantee ahead of time will happen.

However, the time at which he urinates is also critical. Generally speaking, the later, the better. if he couldn’t do it at the time he wanted--let's say that race tactics dictated he stop sooner than he would have preferred--his level would be higher than otherwise. Not that much higher, but now he would be somewhat more vulnerable to the effects of extra puffs and the effects of deyhdration, which might raise his levels higher than anticipated.

Edit: OK, I finally accessed that full paper:

http://sci-hub.la/10.1249/MSS.0b013e3181b2e87d

The urinary levels of slabutamol following a four mg oral dose actually didn't drop that much from 4-8 hours, though there was large individual variation. There was a much larger drop from 8-12 hours:

0-4 hr 2400 ng/ml (estimated from bar graph)
4-8 hr 2200 ng/ml
8-12 hr 1200 ng/ml

Even from these data, though, one can see the potential that urinating during a stage might have on levels at the end of the stage. There was a large amount of individual variation, and 3/10 subjects showed a drop of 50% or more from 0-4 hr to 4-8 hr. Another study by the same group showed, again, a relatively small drop from 0-4 hr vs. 4-8 hr, but an even larger drop to 8-12 hr, about 67%. Still another study, by a different group,reported a drop of about one-third, from about 1650 ng/ml in 0-6 hours to about 1100 in 6-12 hours. So depending on factors such as how long before the stage an oral dose was taken, and the individual, a very large difference is certainly plausible.

 

[hazaran]

The stage had a sizable break let go so he would have peed then, and probably again some time before the finish before it gets too fast. He was the race leader so he kinda gets to decide the time, anyway.

Though I wonder how far you can spin this. Take the 12h dose, don't pee for 12 hours, take another 12h dose, some water and an hour later pee for the test?

I mean WADA (ultimately CAS) wants more than just a test within the parameters, they want you to tell them what you did, then you can do a test replicating more or less that scenario. Might be hard to argue you didn't pee for some 12, 13 hours riding a GT.

 

[Merckx index]

Re:

The stage had a sizable break let go so he would have peed then, and probably again some time before the finish before it gets too fast. He was the race leader so he kinda gets to decide the time, anyway.

Well, he says he has all that information, so it should come out. But even if he decides when as a leader, he hasn't always been a leader throughout all the stages in every GT he's raced, so he has to take that into account.

Though I wonder how far you can spin this. Take the 12h dose, don't pee for 12 hours, take another 12h dose, some water and an hour later pee for the test?

LOL, believe me, I was wondering about that, too. If he could hold it long enough, then that 1600 ug/24 hr rule could help him. Even if he did pee before the 12hr was up, though, I now see from the data I referred to that there would be a significant amount of salbutamol left in his system, enough that it would probably be worth preparing for the test 24 hr in advance. From the two studies by the Elers group, if take 800 ug dose and pee after 8 hours, then after 12 hours, urine has a concentration of about 120-150 ng/ml. If managed to retain the urine for the full twelve hours, the concentration would be 200-250 ng/ml. These are averages, of course, but give an indication of how much retaining would help—in the case of inhaling these relative small amounts, not too much.

I mean WADA (ultimately CAS) wants more than just a test within the parameters, they want you to tell them what you did, then you can do a test replicating more or less that scenario. Might be hard to argue you didn't pee for some 12, 13 hours riding a GT.

This part isn't clear to me. My understanding is that if he just shows that he can inhale 800 ug and get a level of 2000 ng/ml, improbable as that is, he will get off, even if in the race he took it over a long period of time, stopped to pee, etc. This was what I meant by getting off on a technicality.

 

[hazaran]

I was thinking of this interview with Olivier Rabin, science director at WADA:

https://translate.google.com/translate?sl=auto&tl=en&js=y&prev=_t&hl=en&ie=UTF-8&u=http%3A%2F%2Fwww.lemonde.fr%2Fcyclisme%2Farticle%2F2017%2F12%2F14%2Faffaire-froome-la-charge-de-la-preuve-revient-a-l-athlete_5229768_1616656.html&edit-text=&act=url

Though on a second read now it also of course mentions

A urine sample is taken without taking the substance, to have the basic level of the athlete, especially when they are athletes who have chronic treatments. Then, the athlete takes salbutamol under the same conditions that he has described. Then we take at relatively precise hours.

Not sure how fair that is. I guess you can do one test for WADA and if that doesn't get you off, still have another one for CAS.

 

[thehog]

Obviously, a high dose of Salbutamol indicates severe breathing problems. We can all see the footage, and the end result compared to a peloton of athletes in their prime. Used to enhance his performance, and probably miscalculated the max -possibly because of a blood transfusion. I'm eager to find out, but it doesn't matter all that much. He had an unfair advantage, that's what counts.

I don't know when Sky left the mpcc exactly, but it's only the fourth scandal since. You had the rider who came forward about painkiller abuse within the team, the mysterious medical package delivery,TUEs during TDF wins, and now this. Add UCI's reluctance to do their job properly when it involves 35 million, and basicly nothings changed since the US Postal scam.

Were they ever part of the MPCC?

No.

My bad,they rejected to join because ofits medical rules.

Brailsford once said that Sky’s internal rules were more stringent than MPCC hence their reason for not joining :lol: