Clenbuterol & half-life

[Señor_Contador]

Hello all.

The Spanish media is in its usual save-the-Spanish-athlete-who-just-tested-positive mode. Once of the variables they're using in aleging that Contador did not dope was that Contador did not test positive on the 07/20/10 and 07/22/10 tests, while he did on the one done on 07/21/10. Their magic bullet: Clenbuterol has a half-life of 36 hours, thus if he did not test positive on 07/20/10 and 07/22/10 and clenbuterol has a half-life of 36 hours, one can only deduce that what took place on 07/21/10 cannot definitely be described as "doping", but a bad case of the "contaminated steak".

Does microdosing have anything to do with it?

 

[Willy_Voet]

You know what 1/2 life means, right? If the 1/2 life of something is 1 day, it does not take 2 days for it to completely disappear.

edit: picture below for radioactive decay--it applies to drug metabolism as well.

 

[Señor_Contador]

You know what 1/2 life means, right? If the 1/2 life of something is 1 day, it does not take 2 days for it to completely disappear.

edit: picture below for radioactive decay--it applies to drug metabolism as well.

Hello Willy.

I do not understand what you're saying. Could you please tell me in non-scientific language?

I'm sorry but I am very ignorant on the subject.

 

[Ferminal]

Hello Willy.

I do not understand what you're saying. Could you please tell me in non-scientific language?

I'm sorry but I am very ignorant on the subject.

Half-life refers to the time it takes for half the substance to decay, or in this case, half the substance to disappear from the body through metabolism etc.

So if the half-life was 24 hours, and there were 10g to start with, there would be 5g after 24 hours, 2.5g after 48hrs and 1.25g after 72hrs etc etc.

 

[djconnel]

A difference is with radioactive decay the exponential nature of the function is highly precise. With metabolism it's more of an approximation.

However, using the model, if the concentration is 100% now, a day from now it will be (1/2)^(24/36) = 63%.

I'm not sure why this implies food contamination, since whether the ingestion were intentional or not it seems the same time-dependence would apply. The more important conclusion is that this isn't the tail-end of decay from an earlier high dose. Had that been the case, it should have shown up in the test the day prior. So assuming a significant fraction of an ingested dose ends up in the blood, then the concentrations involved here are way too low to enhance performance. Typical "doping doses" are on order 100 μg, with the low end of therapeutic doses around 20 μg, while multiplying the concentration in the sample by a Contador-like body mass results in a net of only 3 μg.

 

[Merckx index]

According to Science of Sport, Contador tested positive on two days, the first on7/21 at 50 pg, the second on 7/22 at 20 pg. He tested negative before the 20th and after the 22d. This is consistent with half-life data.

The 50 pg value is 40x lower than the minimum required performance level (MRPL) required by WADA. So it's clear that however clenbuterol got into AC's system, a) it was taken after 7/20; and b) the amount ingested was far below both the MRPL and a performance-enhancement level. The question is, what does this mean.

There seem to be two main possibilities. One is that it was the result of food contamination, as AC has maintained. The other is that the clenbuterol was present in transfused blood. While not ruling this out, here is an argument against it.

Clenbuterol is metabolized extensively. Thus in animal studies (both cattle and lab animals such as dogs and rats), more than 50% of it was converted into other substances by the time it reached the urine (more precisely, the clenbuterol was labelled with a radioactive isotope, and more than 50% of the isotope was found in other compounds in the urine). This suggests that if AC had taken clenbuterol in larger doses, than withdrew blood containing this clenbuterol and stored it for later transfusion, much of the clenbuterol would have been degraded. How much is difficult to estimate, since the blood would be stored at lower temperatures where metabolism would be slower. However, it appears that much of the degradation in blood takes place non-enzymatically, which means it is less sensitive to temperature.

http://www.fao.org/docrep/w4601e/w4601e06.htm

 

[JRTinMA]

Half-life refers to the time it takes for half the substance to decay, or in this case, half the substance to disappear from the body through metabolism etc.

So if the half-life was 24 hours, and there were 10g to start with, there would be 5g after 24 hours, 2.5g after 48hrs and 1.25g after 72hrs etc etc.

A lot of drugs are non linear, I have no idea if Clenbuterol is linear or non-linear. Pharmador's failed tests make it seem linear based on the numbers presented, 24 hour half life and test value reduced in half over two days. He failed two tests in a row and numbers were thrown around but at that concentration I think its a qual test, not quantitative. The German lab must have made a guess based on same raw data.

 

[Merckx index]

A lot of drugs are non linear, I have no idea if Clenbuterol is linear or non-linear. Pharmador's failed tests make it seem linear based on the numbers presented, 24 hour half life and test value reduced in half over two days. He failed two tests in a row and numbers were thrown around but at that concentration I think its a qual test, not quantitative. The German lab must have made a guess based on same raw data.

I agree that it's probably more qualitative than quantitative. The point is just that the finding of two positives on consecutive days, the second day's lower than the first, is consistent with kinetics. No discrepancy to explain.

As far as I can see, the blood transfusion theory is the only doping explanation that makes sense. He surely did not intentionally ingest clenbuterol in such a tiny dose on 7/20. So it comes down to whether it's plausible that a tiny amount of clenbuterol might have persisted in blood that had been withdrawn earlier, then transfused on the rest day. Since the amount is so tiny, it's hard to rule out, but I'm assuming there wouldn't be a lot in the withdrawn blood to begin with.

 

[mountaindew]

Half-life has nothing to do w/detection time

 

[JRTinMA]

Half-life has nothing to do w/detection time

Drug efficacy and detection time are very different and can be confusing because the curve is very similar for both with Clen, good point.

 

[Merckx index]

Half-life has nothing to do w/detection time

Of course it does. Half-life, as applied to pharmacokinetics, refers to the amount of drug present in the blood, urine, or other tissue/excretion tested over time. A shorter half-life is correlated with a shorter detection time.

Drug efficacy refers to the action of the drug, but this is not relevant to someone who is simply determining the presence of the drug.

 

[djconnel]

According to Science of Sport, Contador tested positive on two days, the first on7/21 at 50 pg, the second on 7/22 at 20 pg. He tested negative before the 20th and after the 22d. This is consistent with half-life data.

It's actually pg/ml, which given the density of blood is reasonably close to 1 g/ml, corresponds to a mass fraction of parts per trillion.

There seem to be two main possibilities. One is that it was the result of food contamination, as AC has maintained. The other is that the clenbuterol was present in transfused blood. While not ruling this out, here is an argument against it.

Clenbuterol is metabolized extensively. Thus in animal studies (both cattle and lab animals such as dogs and rats), more than 50% of it was converted into other substances by the time it reached the urine (more precisely, the clenbuterol was labelled with a radioactive isotope, and more than 50% of the isotope was found in other compounds in the urine). This suggests that if AC had taken clenbuterol in larger doses, than withdrew blood containing this clenbuterol and stored it for later transfusion, much of the clenbuterol would have been degraded. How much is difficult to estimate, since the blood would be stored at lower temperatures where metabolism would be slower. However, it appears that much of the degradation in blood takes place non-enzymatically, which means it is less sensitive to temperature.

http://www.fao.org/docrep/w4601e/w4601e06.htm

Good analysis -- I'd overlooked the transfusion possibility.

I'm not sure why nonenzymatic degradation implies a weak temperature dependence, however. Plenty of processes, chemical or physical, are highly temperature dependent without the presence of enzymes or other catalysts.

 

[mountaindew]

Of course it does. Half-life, as applied to pharmacokinetics, refers to the amount of drug present in the blood, urine, or other tissue/excretion tested over time. A shorter half-life is correlated with a shorter detection time.

Drug efficacy refers to the action of the drug, but this is not relevant to someone who is simply determining the presence of the drug.

Nope. Nadrolone half life 6 days. Detection time 18 months.

 

[Merckx index]

Nope. Nadrolone half life 6 days. Detection time 18 months.

That’s because there is a test for metabolites of the drug, which may persist much longer. In the same way, the biopassport may detect EPO use well after the drug has been metabolized below detectable levels.

So you are correct, that with SOME drugs, detection times do not depend on the half-life of the drug. But this is not the case with most drugs. So the blanket statement, half-life has nothing to do with detection time, simply is not correct. For most drugs the two are closely linked, and that certainly is the case with clenbuterol.

Also, the half-life is of course not the same thing as the detection time. A drug may have a relatively short half-life and a relatively long detection time, if detection methods are highly sensitive. But for any direct test of a drug, the detection time will be correlated with the half-life. For a test of a given sensitivity, any thing that increases the half-life will correspondingly increase the detection time.

 

[DirtyWorks]

crackpot theory #111

Pharmador was taking Clem over a long period of time in micro-doses to evade detection. The reason would be to lose weight while maintaining power. His watts/kilo would improve.

As discussed in other threads I'm too lazy to find, minor differences in weight do big things to watts/kilo. The improvement in watts/kilo meaningfully reduces times up Hors Category climbs.

 

[blackcat]

best explanation by far, is failed mask. Not blood bag.

Aint it a moot point anyhow for purposes of this discussion. Just wanna label him with the doper epithet, well ok, but all who know on this board, realise he is on a truck load of gear, and all these fine print points matter in a potential sanction, not in whether he dopes and one can level the doper epithet.

Other point, clen is STRICT LIABILITY.

Some cats on this thread, are conflating the SOP of the labs, and the testing for their MSGC, which requires them to be able to identify, clen, at 400 times the amount they identified the sample of AC. But, this does not mean, a sample identified, at 0.25 % of that, or 0.0025 that ratio, is any "pass" just like StrongArm's corticosteroid positive in 99

dont conflat the two

 

[indurain666]

There seem to be two main possibilities. One is that it was the result of food contamination, as AC has maintained. The other is that the clenbuterol was present in transfused blood. While not ruling this out, here is an argument against it.

Clenbuterol is metabolized extensively. Thus in animal studies (both cattle and lab animals such as dogs and rats), more than 50% of it was converted into other substances by the time it reached the urine (more precisely, the clenbuterol was labelled with a radioactive isotope, and more than 50% of the isotope was found in other compounds in the urine). This suggests that if AC had taken clenbuterol in larger doses, than withdrew blood containing this clenbuterol and stored it for later transfusion, much of the clenbuterol would have been degraded. How much is difficult to estimate, since the blood would be stored at lower temperatures where metabolism would be slower. However, it appears that much of the degradation in blood takes place non-enzymatically, which means it is less sensitive to temperature.

http://www.fao.org/docrep/w4601e/w4601e06.htm

I thought about your second hypothesis a few hours ago: Alberto does clen during the off season to shed some pounds, really the anabolic effect of clen is not great.. Stores the blood and then uses it assuming that a metabolic "rule of thumb" is that the clen concentration exponentially or discretely decays to non detectable limits after a few days.

Physically this would explain a lot, however, why would he use clen of all PEDs? these guys get tested year round, Alberto doesn't seem to have too many problems losing weight.

We are still missing something here or this is purely bad luck or sabotage.

 

[indurain666]

best explanation by far, is failed mask. Not blood bag.

Best explanation if you are not a very educated, logical and reasonable individual. I have asked this several times today, could you please explain how do you mask clenbuterol?

You may have a point, but we need some facts.

 

[Barrus]

Pharmador was taking Clem over a long period of time in micro-doses to evade detection. The reason would be to lose weight while maintaining power. His watts/kilo would improve.

As discussed in other threads I'm too lazy to find, minor differences in weight do big things to watts/kilo. The improvement in watts/kilo meaningfully reduces times up Hors Category climbs.

as far as I know microdosing does not work with clen

 

[bike_framed]

I have asked this several times today, could you please explain how do you mask clenbuterol?

You may have a point, but we need some facts.

According to Professor Michel Audrun, one of the founders of the UCI’s Biological Passport system: “it cannot be masked like other products."

http://www.velonation.com/News/ID/5...Damsgaard-Michel-Audrun-and-riders-react.aspx

 

[blackcat]

yeah, but Ashenden himself, does not know everything neither.

I know some big riders used clen. IN RACING.

They dont use a product in racing that shows up, defeats the point if they are gonna get caught.

So, they have techniques to manage to pass tests. Whether catheter, or other methods.

And Indurain, dont be a douche

 

[BroDeal]

A study about testing Clen levels in humans after eating beef injected with the drug (PDF):

http://proceedings.live-record.de/proceedings_2_pdf/2_185.pdf

It is just a few pages long.

 

[mountaindew]

That’s because there is a test for metabolites of the drug, which may persist much longer. In the same way, the biopassport may detect EPO use well after the drug has been metabolized below detectable levels.

So you are correct, that with SOME drugs, detection times do not depend on the half-life of the drug. But this is not the case with most drugs. So the blanket statement, half-life has nothing to do with detection time, simply is not correct. For most drugs the two are closely linked, and that certainly is the case with clenbuterol.

Also, the half-life is of course not the same thing as the detection time. A drug may have a relatively short half-life and a relatively long detection time, if detection methods are highly sensitive. But for any direct test of a drug, the detection time will be correlated with the half-life. For a test of a given sensitivity, any thing that increases the half-life will correspondingly increase the detection time.

Makes sense.

 

[blackcat]

A study about testing Clen levels in humans after eating beef injected with the drug (PDF):

http://proceedings.live-record.de/proceedings_2_pdf/2_185.pdf

It is just a few pages long.

possible, but beyond all reasonable estimation.

thanks bro

 

[Merckx index]

A study about testing Clen levels in humans after eating beef injected with the drug (PDF):

http://proceedings.live-record.de/proceedings_2_pdf/2_185.pdf

It is just a few pages long.

This is very interesting. At first the volunteers tested negative for clenbuterol, but this was because the test was relatively insensitive. Upon using a more sensitive test, they found clenbuterol concentrations as high as 850 pg/ml. in urine--almost 20x what AC's value was. In fact, all four subjects who were analyzed more carefully had values of > 100 pg. 22-46 hours after the meat consumption. IMO, this strongly supports food contamination as a viable explanation. IOW, it has to be taken seriously, though there are other explanations.

They also note that "a 300 g meal would resemble an intake of 1.2 ug clenbuterol." This suggests yet another possibility. AC could have ingested clenbuterol in contaminated meat not at the Tour, but at some earlier time. Then he could have withdrawn blood and re-infused at the Tour. There could have been enough clenbuterol in the transfused blood to account for the low value in his urine.