- May 31, 2010
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It looks like Ulissi took his normal 2 puffs on stages 5 & 8 which he won and then increased his dose on Stage 11 thinking he wouldn't be tested, but he was ! Somehow they caught him (randomly?) because on that day he came 4:31 in arrears...and he was far down in the GC.
Then he keeps riding 5 more stages and quits the Giro...
Then he keeps riding 5 more stages and quits the Giro...
- May 11, 2013
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Re:
Actually I remember all that Giro he was amazing, the day after the positive he finished second on a 42 km ITT. It felt like Santambrogio one year before. But of course Salbutamol has no performance enhancing effect same with Froome who came back from the dead with a few extra puffs in Vuelta.
70kmph said:
Actually I remember all that Giro he was amazing, the day after the positive he finished second on a 42 km ITT. It felt like Santambrogio one year before. But of course Salbutamol has no performance enhancing effect same with Froome who came back from the dead with a few extra puffs in Vuelta.
- May 11, 2013
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Re: Re:
As far as I know, second place in a stage is not tested so he might've been high on salbutamol even the next day whereas his positive came due to bad luck as in randomly selected or a targeted test as he finished 58th on that particular stage.
ClassicomanoLuigi said:
As far as I know, second place in a stage is not tested so he might've been high on salbutamol even the next day whereas his positive came due to bad luck as in randomly selected or a targeted test as he finished 58th on that particular stage.
- May 31, 2010
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Petacchi doping controls in 2007 Giro d’Italia
Stage/Alleged Dose/Urine
3 400 498
7 400 425
11 700 1352
18 400 537
21 400 399
He is using 4 times more Salb than Ulissi during the race
His punishment was greater
They will see Froome longitudinal numbers and get an idea of his average intake
Stage/Alleged Dose/Urine
3 400 498
7 400 425
11 700 1352
18 400 537
21 400 399
He is using 4 times more Salb than Ulissi during the race
His punishment was greater
They will see Froome longitudinal numbers and get an idea of his average intake
70kmph said:
I don't believe those alleged doses. His urine values are too high for them. Lab studies have shown that the majority of subjects don't have values those high even with 800 ug, and these are studies that maximize detected levels by inhaling all of the drug at once, and taking urine samples within several hours later. In any case, if Petacchi was getting urine levels that high from taking 400 ug, he would have to know he had a very good chance of exceeding the threshold if he took the allowed dose of 800 ug, or even the 700 ug he claimed to have taken. If his urine values were typically that high after 400 ug, he should have notified UCI and told them he was concerned he might be an outlier who could exceed the threshold without taking more than the allowed dose. But I do wonder why he would tell the panel he took 700 ug,, since 800 ug would have helped his case a little more, and I don't see how anyone would know the difference.
His USG was very high the day he tested over the threshold, 1.033, reflecting the fact that it was very hot, 34 degrees reported at one point. But as far as I can tell, temperatures were lower for the other stages, and i doubt his USG was anywhere near that high.
- May 31, 2010
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One of the difficulties is cannot find Pettachi's controlled pharmacokinetic study
Maybe its part of his private medical record
That would help
PS: Petacchi had an Abbreviated Therapeutic Use Exemption (ATUE) from the UCI, which allowed him to take three doses of 200 mcg of Salbutamol by inhalation
Maybe its part of his private medical record
That would help
PS: Petacchi had an Abbreviated Therapeutic Use Exemption (ATUE) from the UCI, which allowed him to take three doses of 200 mcg of Salbutamol by inhalation
As the immediately preceding posts indicate, one of the outstanding questions raised by salbutamol positives, not only Froome’s, but also Ulissi’s and Petacchi’s, is how a rider could go so far over the threshold one time, after numerous tests in which he was well below the threshold. Here’s an hypothesis that might explain it.
Salbutamol is commonly taken as a racemic mixture of (R-) and (S+) forms. The R-form is the one that interacts with B2-adrenergic receptors to relieve broncho-constriction. The S-form is inactive at these receptors. Because of this, levosalbutamol, a preparation of salbutamol consisting entirely of the R-form (levo refers to the fact that this stereoisomer rotates polarized light to the left; R vs. S is an alternate designation based on the 3-D conformations of the isomers) is more potent than the racemic mixture. Since the racemic mixture is 50/50, one would expect a preparation of pure R form to be twice in potent. In fact, thought, it’s generally even stdronger, because the S-form is known to have negative effects in the lungs. When an asthmatic takes a racemic mixture, part of the R-form in effect may be required to overcome these negative effects.
E.g., one study reported that 0.63 mg of levosalbutamol was as clinically effective as 2.5 mg—four times the dose—of the racemic mixture. Not all studies have reported this effect, and it appears that it’s more likely to be observed over the long-term, under which conditions the S-form is gradually accumulating to some extent in the lungs. But at a minimum, the pure R-form is at least twice as potent per mg as the S-form.
Most of these studies have been carried out with subjects inhaling the drug, since that’s the main clinical use. But there have been some studies of oral levosalbutamol, which also indicate that it’s more potent than the racemic mixture in inducing various pharmacological effects. So presumably whatever PE effects salbutamol has, they're induced by the R form.
This is very significant, because it means an athlete could take at least twice the dose of levosalbutamol as the racemic mixture without exceeding the threshold. E.g., if on average, the athlete found he could take a maximum oral dose of 2 mg of the racemic mixture over a few hours without exceeding the threshold, he could raise that to 4 mg of the R form. In fact, some scientists have pointed this out, as a potential loophole, so to speak, in the doping rules.
There’s another important difference, though. When salbutamol is taken orally, or by some other route than inhalation, the primary means of metabolism is sulfation. The R-form is sulfated more quickly than the S-form, which means it’s cleared from the blood and goes into the urine more quickly. One study, in which the substances were given IV, found that the half life in the blood of the R form was about 2.5 hr, vs. 4.7 hr for the S-form.
This could be a problem for someone orally dosing with the drug, since initially higher concentrations of it would appear in the urine. But whether it was a disadvantage would depend on factors such as how long before giving a urine sample he dosed, and whether or how often he was able to urinate. If a rider orally dosed upon waking up on the day of a race or stage that started around noon, was able to urinate during the race, then gave a sample in the late afternoon at the end of the race, he would probably have a lower urinary level than if he took a racemic mixture.
Because of all these factors, I can’t estimate any numbers, but I think it’s reasonable to conclude that a rider might take several times the usual dose of salbutamol in the form of the R form without worrying about exceeding the threshold. I think everyone can now see where I’m going with this. Suppose he runs out of levosalbutamol, and either doesn’t immediately realize that, or does, but simply forgets, from habit, to lower his dose accordingly. Suddenly, he’s effectively increased his dose by several-fold over what is safe. Or maybe he goes in the other direction, switching from racemic to levosalbutamol, and forgets--or maybe doesn't even appreciate--that the timing of doses and urination are now more critical. At the least, the more such factors that have to be paid attention to, the greater potential for a mistake.
Finally, there’s one other important effect at play here. The enantiomers test, which is supposed to distinguish inhaled from oral doses (though in practice only distinguishes inhaled doses within the allowed limit from oral doses), of course assumes that the athlete is taking the racemic mixture. When the dose is inhaled, the ratio of S/R is generally < 2.5, whereas oral doses have a larger S/R ratio. This high S/R ratio of oral doses reflects the fact that, as noted above, the R form, when it goes to the gut, is metabolized (mostly sulfated), so less of the unmetabolized or free form is present in the urine. When salbutamol is inhaled, in contrast, relatively little of it is thought to be metabolized in the lungs, so the S/R ratio of the substance passing into the urine is initially close to unity. It rises over time, as some of the inhaled substance which is swallowed becomes metabolized.
So if an athlete does take the R form, he will obviously have a very low S/R ratio (not zero, because a small portion of it is converted in the body to the S form). So while using the R form can not only allow an athlete to take larger doses while maintaining urinary levels below the threshold, but also allow him to exhibit a very low S/R ratio, and thus appear by the enantiomers test to be inhaling.
http://sci-hub.la/10.1517/14656566.7.12.1659
http://sci-hub.la/10.2165/00003088-200140010-00003
https://www.ncbi.nlm.nih.gov/pubmed/9284849
Salbutamol is commonly taken as a racemic mixture of (R-) and (S+) forms. The R-form is the one that interacts with B2-adrenergic receptors to relieve broncho-constriction. The S-form is inactive at these receptors. Because of this, levosalbutamol, a preparation of salbutamol consisting entirely of the R-form (levo refers to the fact that this stereoisomer rotates polarized light to the left; R vs. S is an alternate designation based on the 3-D conformations of the isomers) is more potent than the racemic mixture. Since the racemic mixture is 50/50, one would expect a preparation of pure R form to be twice in potent. In fact, thought, it’s generally even stdronger, because the S-form is known to have negative effects in the lungs. When an asthmatic takes a racemic mixture, part of the R-form in effect may be required to overcome these negative effects.
E.g., one study reported that 0.63 mg of levosalbutamol was as clinically effective as 2.5 mg—four times the dose—of the racemic mixture. Not all studies have reported this effect, and it appears that it’s more likely to be observed over the long-term, under which conditions the S-form is gradually accumulating to some extent in the lungs. But at a minimum, the pure R-form is at least twice as potent per mg as the S-form.
Most of these studies have been carried out with subjects inhaling the drug, since that’s the main clinical use. But there have been some studies of oral levosalbutamol, which also indicate that it’s more potent than the racemic mixture in inducing various pharmacological effects. So presumably whatever PE effects salbutamol has, they're induced by the R form.
This is very significant, because it means an athlete could take at least twice the dose of levosalbutamol as the racemic mixture without exceeding the threshold. E.g., if on average, the athlete found he could take a maximum oral dose of 2 mg of the racemic mixture over a few hours without exceeding the threshold, he could raise that to 4 mg of the R form. In fact, some scientists have pointed this out, as a potential loophole, so to speak, in the doping rules.
There’s another important difference, though. When salbutamol is taken orally, or by some other route than inhalation, the primary means of metabolism is sulfation. The R-form is sulfated more quickly than the S-form, which means it’s cleared from the blood and goes into the urine more quickly. One study, in which the substances were given IV, found that the half life in the blood of the R form was about 2.5 hr, vs. 4.7 hr for the S-form.
This could be a problem for someone orally dosing with the drug, since initially higher concentrations of it would appear in the urine. But whether it was a disadvantage would depend on factors such as how long before giving a urine sample he dosed, and whether or how often he was able to urinate. If a rider orally dosed upon waking up on the day of a race or stage that started around noon, was able to urinate during the race, then gave a sample in the late afternoon at the end of the race, he would probably have a lower urinary level than if he took a racemic mixture.
Because of all these factors, I can’t estimate any numbers, but I think it’s reasonable to conclude that a rider might take several times the usual dose of salbutamol in the form of the R form without worrying about exceeding the threshold. I think everyone can now see where I’m going with this. Suppose he runs out of levosalbutamol, and either doesn’t immediately realize that, or does, but simply forgets, from habit, to lower his dose accordingly. Suddenly, he’s effectively increased his dose by several-fold over what is safe. Or maybe he goes in the other direction, switching from racemic to levosalbutamol, and forgets--or maybe doesn't even appreciate--that the timing of doses and urination are now more critical. At the least, the more such factors that have to be paid attention to, the greater potential for a mistake.
Finally, there’s one other important effect at play here. The enantiomers test, which is supposed to distinguish inhaled from oral doses (though in practice only distinguishes inhaled doses within the allowed limit from oral doses), of course assumes that the athlete is taking the racemic mixture. When the dose is inhaled, the ratio of S/R is generally < 2.5, whereas oral doses have a larger S/R ratio. This high S/R ratio of oral doses reflects the fact that, as noted above, the R form, when it goes to the gut, is metabolized (mostly sulfated), so less of the unmetabolized or free form is present in the urine. When salbutamol is inhaled, in contrast, relatively little of it is thought to be metabolized in the lungs, so the S/R ratio of the substance passing into the urine is initially close to unity. It rises over time, as some of the inhaled substance which is swallowed becomes metabolized.
So if an athlete does take the R form, he will obviously have a very low S/R ratio (not zero, because a small portion of it is converted in the body to the S form). So while using the R form can not only allow an athlete to take larger doses while maintaining urinary levels below the threshold, but also allow him to exhibit a very low S/R ratio, and thus appear by the enantiomers test to be inhaling.
http://sci-hub.la/10.1517/14656566.7.12.1659
http://sci-hub.la/10.2165/00003088-200140010-00003
https://www.ncbi.nlm.nih.gov/pubmed/9284849
- Mar 29, 2016
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Re: Re:
So is born the "Uncle Brian at UCI will sort this out" theory ... otherwise it's a Sky doc c**k up.ClassicomanoLuigi said:
Would have to be a Lappartient theory surely?
7th Sept - Sample given
20th Sept - A Sample notification to Froome
21st Sept - Presidential Election
~12th October Froome's notification of B Sample AAF
13th December A & B AAF Announced by UCI after Le Monde & Guardian Story and Sky press release in morning.
So normal WADA results management procedure timings, seem to have been followed between 7th Sept & 21st Sept as the A sample was analysed and notification given to Chris Froome before UCI Election. B sample analysis would then have been requested by Froome and complete some time 'after' the UCI election result within 10 days iirc with B Sample notification to Froome by 12th October? That seems to be inline with WADA results management procedure and timings.
Things only seem to be seriously delayed more than WADA guidelines would suggest after Lappartient is in power and B sample result is known surely? As MI has confirmed, B sample should come back no more than 10 days after analysis, so at maximum UCI should have announced sometime in October or as soon as Froome confirmed he is going to explain AAFs or not challenge them and accept a sanction. That would be late October, early November at latest in terms of the rules, not December surely?
7th Sept - Sample given
20th Sept - A Sample notification to Froome
21st Sept - Presidential Election
~12th October Froome's notification of B Sample AAF
13th December A & B AAF Announced by UCI after Le Monde & Guardian Story and Sky press release in morning.
So normal WADA results management procedure timings, seem to have been followed between 7th Sept & 21st Sept as the A sample was analysed and notification given to Chris Froome before UCI Election. B sample analysis would then have been requested by Froome and complete some time 'after' the UCI election result within 10 days iirc with B Sample notification to Froome by 12th October? That seems to be inline with WADA results management procedure and timings.
Things only seem to be seriously delayed more than WADA guidelines would suggest after Lappartient is in power and B sample result is known surely? As MI has confirmed, B sample should come back no more than 10 days after analysis, so at maximum UCI should have announced sometime in October or as soon as Froome confirmed he is going to explain AAFs or not challenge them and accept a sanction. That would be late October, early November at latest in terms of the rules, not December surely?
Exactly, so any unnecessary delay / reason for not knowing yet, if you are suspicious UCI are covering up Froome's AAF will apply to Lappartient surely? I agree, nobody should know anything about this case until the final decision and so I don't think anything is being covered up.
Re:
Don't worry about this aspect of proceedings. I'd say that Sky and Froome overdosed banking on Uncle Brian winning the upcoming election. He did after all think he had it in the bag. The election that is.
samhocking said:
Don't worry about this aspect of proceedings. I'd say that Sky and Froome overdosed banking on Uncle Brian winning the upcoming election. He did after all think he had it in the bag. The election that is.
So Uncle Brian is notifying Froome of the AAF he will never have to answer? Is that not like a corrupt policeman filling you out a speeding ticket and giving it to the magistrate even though he's accepted money to not issue you with a ticket? WADA has to be notified of the result at some point, AAFs can't simply be deleted off an athletes ADAMS file you know because UCI don't have the access to do that.
- May 31, 2010
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Another case that's even more obscure was rider Piepoli after winning stage 10 of the Giro 2007
Piepoli was over threshold on the same day as Petacchi, Stage 11
A different rider, a small climber he gets inadvertently tested on a flat stage like Ulissi using a high dose of
Salbutamol 1800ng/ml
His sample was sent out for the enantiomers to same Barcelona lab but result was undetermined
He claimed not to know how many puffs he used and blamed a faulty inhaler
Piepoli was over threshold on the same day as Petacchi, Stage 11
A different rider, a small climber he gets inadvertently tested on a flat stage like Ulissi using a high dose of
Salbutamol 1800ng/ml
His sample was sent out for the enantiomers to same Barcelona lab but result was undetermined
He claimed not to know how many puffs he used and blamed a faulty inhaler
ClassicomanoLuigi said:
Which tends to indicate that the majority of the Salbutamol was already in his system. When you are wheezing badly you are not counting puffs. If Froome actually needed that much Salbutamol immediately before the stage, during and after he would have been using the Ventolin puffer constantly and his performance would have been a bad one. Froome has already indicated that scenario didn't happen. Froome's story is not plausible as it doesn't coincide with the test result, not even close. The only alternative is that the testing result is flawed or completely wrong. Froome's defense team can't scientifically explain the result based on Froome's statement so their only recourse will be to attack the testing methods themselves or create enough doubt to at least make the result questionable. Simple denial or bluff won't stop a suspension.
70kmph said:Another case that's even more obscure was rider Piepoli after winning stage 10 of the Giro 2007
Piepoli was over threshold on the same day as Petacchi, Stage 11
A different rider, a small climber he gets inadvertently tested on a flat stage like Ulissi using a high dose of
Salbutamol 1800ng/ml
His sample was sent out for the enantiomers to same Barcelona lab but result was undetermined
He claimed not to know how many puffs he used and blamed a faulty inhaler
Targeted testing?
His blood would have had all the plasma removed surely before storage so no chance of any substance being transfused back again? I guess theoretically there could be the tiniest trace amount after being centrifuged, aka Contador if we believe that was a transfusion, but I can't believe Sky would be risking storing, transporting and transfusing raw blood? And anyway the transfusion is diluted down with the other 5 litres.
samhocking said:
Blood bags have already been ruled out or beyond the realms of possibility by a number of cycling drs and previously in this thread as explained by MI due to the dilution factor.
thehog
BANNED
- Jul 27, 2009
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bigcog said:
Doctors in general, yes but not the doctors who understand cycling or how transfusions work within a doping context.
It cannot be ruled out at this point however unlikely it may have been.
Salbutamol is often used if a patient reacts poorly to a blood transfusion via a nebulizer whether a asthmatic or not.
It doesn't help the case you're trying to make by adding more and more absurd elements. Unless he had his blood bag during the actual race, no, salbutamol in that is still not the answer.
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