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Thanks!
Not sure about that. Just listen to the podcast of Watt Police with Soren Schifter (Biopharma/Pharma investment, MD, DMSc. - Specialist in clinical physiology and nuclear medicine - Expertise in preclinical and clinical drug development). Daprodustat has a half-life between 1-4 hours. Just a tablet... On top of that, the drug is quite new. You need to develop a specific assay for it (includes sample prep, reagens, conditions, detection, analysis,...). How long did it take to detect EPO?
I watched the podcast & thought maybe Schifter was going to discuss designer HIFs that would actually be undetectable. If I understand him correctly, he acknowledges there's tests for the current HIFs, but doesn't think they're very reliable? (he does do an excellent job of explaining the pharmacology of these compounds).
Roxadustat (FG-4592), Vadadustat & Daprodustat are all hypoxia inducible factors (HIF) that WADA has testing assays for:
https://pubmed.ncbi.nlm.nih.gov/26361079/
According to the literature, Roxadustat has a detection window of up to 167 hrs - about 1 week after the last dose (normal use). On the ABP, normal use will push hematological values up to - but not exceed - upper threshold limits (however, that's enough suspicion to warrant target testing I would think).
Before Roxadustat was even approved by the FDA for clinical use, dopers were getting their hands on it & a few cyclists even tested positive:
A Drug Hits Cycling Before It Hits the Market (Published 2015)
FG-4592, which increases production of red blood cells, is not approved for human consumption but nonetheless has led to two positive tests just this month.
Here's the top tennis star Schifter was referring to:
Former world No. 1 tennis star Halep provisionally suspended for doping
Two-times major winner Simona Halep of Romania has been provisionally suspended after testing positive for the banned substance roxadustat, the International Tennis Integrity Agency (ITIA) said on Friday.
www.france24.com
So, dopers using an HIF could stop usage about 1 week before their competition & probably avoid testing positive. However, the risk of testing positive with OOC/target testing during thier training build-up phase would be very high. Plus samples would be stored for the next 10 yrs for any retesting.
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Thanks for the extra explanation. As I'm not a native English speaker, can you explain me what you mean with the abbreviation ABP?I watched the podcast & thought maybe Schifter was going to discuss designer HIFs that would actually be undetectable. If I understand him correctly, he acknowledges there's tests for the current HIFs, but doesn't think they're very reliable? (he does do an excellent job of explaining the pharmacology of these compounds).
Roxadustat (FG-4592), Vadadustat & Daprodustat are all hypoxia inducible factors (HIF) that WADA has testing assays for:
https://pubmed.ncbi.nlm.nih.gov/26361079/
According to the literature, Roxadustat has a detection window of up to 167 hrs - about 1 week after the last dose (normal use). On the ABP, normal use will push hematological values up to - but not exceed - upper threshold limits (however, that's enough suspicion to warrant target testing I would think).
Before Roxadustat was even approved by the FDA for clinical use, dopers were getting their hands on it & a few cyclists even tested positive:
A Drug Hits Cycling Before It Hits the Market (Published 2015)
FG-4592, which increases production of red blood cells, is not approved for human consumption but nonetheless has led to two positive tests just this month.www.nytimes.com
Here's the top tennis star Schifter was referring to:
Former world No. 1 tennis star Halep provisionally suspended for doping
Two-times major winner Simona Halep of Romania has been provisionally suspended after testing positive for the banned substance roxadustat, the International Tennis Integrity Agency (ITIA) said on Friday.
So, dopers using an HIF could stop usage about 1 week before their competition & probably avoid testing positive. However, the risk of testing positive with OOC/target testing during thier training build-up phase would be very high. Plus samples would be stored for the next 10 yrs for any retesting.
If I'm not mistaken, Daprodustat would have a half-life of 1-4 hours. So, much less than Roxadustat (at least 4 times faster breakdown). So, that would mean it could be detected for max 1-2 days.
I agree that samples can be stored 10 years for retesting, but if the half-life is 1-4 hours, I don't think they will be able to detect after 10 years...
Athlete Biological Passport. The idea is, that they check values in urine and blood for changes which you wouldn't see in a clean rider.
Ah ok. The Biological Passport. Thx.
Didn't know the abbreviation.
As I understood, also this passport has some loopholes. Going so frequently on altitude training camps would be a logical explanation for higher hemoglobine concentrations.
So, imagine boosting the hemoglobine content even more by using HIFs, and explaining these variations in the ABP by referring to altitude training. Ideal alibi...
That plus some euros changing hands would explain everything.
Yes, according to the available data from the PK studies of the clinical trials, detection of these substances seems pretty trivial (If you can call LC-MS/MS trivial) with a relatively long glow time.I watched the podcast & thought maybe Schifter was going to discuss designer HIFs that would actually be undetectable. If I understand him correctly, he acknowledges there's tests for the current HIFs, but doesn't think they're very reliable? (he does do an excellent job of explaining the pharmacology of these compounds).
Roxadustat (FG-4592), Vadadustat & Daprodustat are all hypoxia inducible factors (HIF) that WADA has testing assays for:
https://pubmed.ncbi.nlm.nih.gov/26361079/
According to the literature, Roxadustat has a detection window of up to 167 hrs - about 1 week after the last dose (normal use). On the ABP, normal use will push hematological values up to - but not exceed - upper threshold limits (however, that's enough suspicion to warrant target testing I would think).
Before Roxadustat was even approved by the FDA for clinical use, dopers were getting their hands on it & a few cyclists even tested positive:
A Drug Hits Cycling Before It Hits the Market (Published 2015)
FG-4592, which increases production of red blood cells, is not approved for human consumption but nonetheless has led to two positive tests just this month.
Here's the top tennis star Schifter was referring to:
Former world No. 1 tennis star Halep provisionally suspended for doping
Two-times major winner Simona Halep of Romania has been provisionally suspended after testing positive for the banned substance roxadustat, the International Tennis Integrity Agency (ITIA) said on Friday.
So, dopers using an HIF could stop usage about 1 week before their competition & probably avoid testing positive. However, the risk of testing positive with OOC/target testing during thier training build-up phase would be very high. Plus samples would be stored for the next 10 yrs for any retesting.
That's a good point since all of the positives for HIFs have been for Roxadustat (in addition to those two cyclists & the tennis player, there's been a few in athletics).
And being an oral compound might be more appealing to a doper that's not thrilled about doing EPO injections or dealing with the logistics of blood transfusions.
Yes, if altitude exposure is of sufficient height & duration, it can cause an abnormal blood profile score.
Altitude is a confounding factor that anti-doping experts look at when evaluating ABP profiles that have been flagged with athletes training at altitude:
Altitude training causes haematological fluctuations with relevance for the Athlete Biological Passport - PubMed
The impact of altitude training on haematological parameters and the Athlete Biological Passport (ABP) was evaluated in international-level elite athletes. One group of swimmers lived high and trained high (LHTH, n = 10) for three to four weeks at 2130 m or higher whereas a control group (n =...
pubmed.ncbi.nlm.nih.gov
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could they also dilute like they did back in the day with EPO, like get a bag of saline to make it less detectable?I watched the podcast & thought maybe Schifter was going to discuss designer HIFs that would actually be undetectable. If I understand him correctly, he acknowledges there's tests for the current HIFs, but doesn't think they're very reliable? (he does do an excellent job of explaining the pharmacology of these compounds).
Roxadustat (FG-4592), Vadadustat & Daprodustat are all hypoxia inducible factors (HIF) that WADA has testing assays for:
https://pubmed.ncbi.nlm.nih.gov/26361079/
According to the literature, Roxadustat has a detection window of up to 167 hrs - about 1 week after the last dose (normal use). On the ABP, normal use will push hematological values up to - but not exceed - upper threshold limits (however, that's enough suspicion to warrant target testing I would think).
Before Roxadustat was even approved by the FDA for clinical use, dopers were getting their hands on it & a few cyclists even tested positive:
A Drug Hits Cycling Before It Hits the Market (Published 2015)
FG-4592, which increases production of red blood cells, is not approved for human consumption but nonetheless has led to two positive tests just this month.
Here's the top tennis star Schifter was referring to:
Former world No. 1 tennis star Halep provisionally suspended for doping
Two-times major winner Simona Halep of Romania has been provisionally suspended after testing positive for the banned substance roxadustat, the International Tennis Integrity Agency (ITIA) said on Friday.
So, dopers using an HIF could stop usage about 1 week before their competition & probably avoid testing positive. However, the risk of testing positive with OOC/target testing during thier training build-up phase would be very high. Plus samples would be stored for the next 10 yrs for any retesting.
I don't think they need to dilute. Using CO rebreathers they can monitor the hemoglobine content so well, that they can go up to the edge.
Allowing CO rebreathers is opening the doors for abuse. By finetuning (read microdosing) they can be where they want to be: the sweet spot!
Yep. Rebreathers could indeed be used just to monitor, while they use microdosing of HIFs with a short half-life to reach the limits in terms of hemoglobine content. Possible Scenario.
Like Venge 82 said they probably don't need to dilute.
Something interesting with the ABP is this paper that showed hyperhydration (about 1 liter of water) consumed before testing reduces ABP Off-Score & ABP sensitivity while using an ESA.
https://pubmed.ncbi.nlm.nih.gov/25773052/
Is there a thread already on Carbon Monoxide (re)breathing / inhalation?
Seems to be a big thing currently. But I'd like to understand what's really known already
Does it basically work as a replacement of altitude training?
Does it "only" increase red cells, or are there additional affects?
How sure is it, it really works?
Seems to be a big thing currently. But I'd like to understand what's really known already
Does it basically work as a replacement of altitude training?
Does it "only" increase red cells, or are there additional affects?
How sure is it, it really works?
Is Lugworm Blood The Next Doping Frontier? | Wild Air Sports
Haemoglobin extracted from lugworms could be a new doping substance for sports performance enhancement. Here is what we know.
wildairsports.com
Interesting lecture as well...
Teams claim they use the CO rebreather for testing purposes only. The CO rebreather can be used to measure the total hemoglobine content (not necessarily the concentration as that depends on the hydration level). So, Teams can monitor the effects of altitude training on the hemoglobine content. So far so good.
But, it could potentially also be used to monitor microdosing of HIFs. These drugs cause the body to produce more EPO (the body's own EPO).
Another use of the CO rebreather could be not for testing purposes, but to boost the body to produce more hemoglobine. CO binds to hemoglobin much faster than oxyen. There will be a shortage of oxygen transport to the muscles. So, the body will be forced to produce more hemoglobine in order to have a better oxygen transport.
That's in a nutshell what I know.
Just wanted to reiterate that altitude training doesn't actually work in any significant way. They probably mainly do it masks unreasonable blood values (and because they think it works or even just might work, and athletes are stupid like that - they'll happily swallow any and all placebos).
Exactly ... the altitude training works just enough that there's plausibility in ridiculous blood values.
All of that stuff is just a giant smokescreen to let them jack up the blood values to the absolute limits of plausible deniability. Always has been, always will be.
Go to altitude camp, train hard, tweet about how they're using the newest 'marginal gain' snake oil fad this year and regardless of how it actually goes results-wise they'll just compensate with the ol' Magic Mix and sprinkle a little extra on top for good measure and then when the rider is doing his victory interview later in the year he can just flash a smug smirk and say "You know, it's been a good year... training camp went really well, the snake oil also seems to be helping with last year's irrelevant issue that I over-exaggerated because I came in second. I feel great at the moment!" and no alarm bells are ringing anywhere with the adoring fans.
You ask if they're over the top? Let's put it this way: If you combine Soudal Quick-Step, Alpecin-Deceuninck, and Team Visma-Lease a Bike's wins in the WorldTour this year they would only equal UAE.
After Wellens smashed it today, and Großschartner basically matched Vingegaard, UAE is up to 33 WorldTour wins this season. Last year, Visma had a crazy 37. UAE is set to easily beat that by some margin. The next most winning team is a four-way tie between SQS, Alpecin, Visma, and Lidl-Trek. They all have 11 wins.
Visma was a dominant force last season, but it was nowhere even remotely close to what we're seeing from UAE this season. This is some utterly historic dominance. Never ever witnessed anything like it.
After Wellens smashed it today, and Großschartner basically matched Vingegaard, UAE is up to 33 WorldTour wins this season. Last year, Visma had a crazy 37. UAE is set to easily beat that by some margin. The next most winning team is a four-way tie between SQS, Alpecin, Visma, and Lidl-Trek. They all have 11 wins.
Visma was a dominant force last season, but it was nowhere even remotely close to what we're seeing from UAE this season. This is some utterly historic dominance. Never ever witnessed anything like it.
Early days still at the Vuelta, but can we conclude that UAE have dialled it back a bit?
Aside from the prologue win UAE have been pretty invisible and only Almeida survived yesterday.
Aside from the prologue win UAE have been pretty invisible and only Almeida survived yesterday.
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