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What the newest salbutamol study means for Froome

Peter Stuart
11 May 2018

Froome’s salbutamol defence grows stronger with new study that claims WADA’s test for salbutamol is fundamentally flawed

A recent study has added further strength to Chris Froome’s defence against a possible sanction over an Adverse Analytical Finding (AAF) for excessive levels of salbutamol in his urine, by claiming the testing system is fundamentally flawed.

Froome exceeded the permitted limit of salbutamol in his urine, set at 1,000ng/ml. Froome registered a concentration of 2,000ng/ml. The 1,000ng/ml limit is intended to reflect a maximum dosage of 1,600 micrograms per 24 hours.

It is accepted that the relationship between the dosage and the reading is not a linear one (according to this study, for instance) though it has been believed that a permitted dosage could not lead to an adverse finding.

Initially reported by The Times, a study published in the British Journal of Clinical Pharmacology called ‘Futility of current urine salbutamol doping control’, claims that in fact a permitted dosage could create a urine concentration high enough to trigger an AAF.

Specifically, the researchers performed simulations based on literature about the absorption of the drug in humans and dogs. According to that simulation, 15.4% of tests resulted in the violation of the 1,000ng/ml limit despite the dosage being within the permitted parameters.

This study comes after a recent revision to Froome’s AAF. Under new WADA rules, a compensation has been made for urine concentration and dehydration, under which Froome’s level has been lowered to 1,429ng/ml rather than 2,000ng/ml. It’s still well north of the 1,000ng/ml limit, though.

Froome’s defence is currently being led by Mike Morgan, a London-based lawyer who successfully defended Lizzie Deignan from a possible ban from three ‘whereabouts’ violations in 2016.

The burden of proof of innocence has, in this case, been placed on the defence rather than WADA investigating the possibility of an inaccurate finding. Hence speculation that Team Sky is preparing its own pharmacokinetic study to replicate his AAF under permitted dosages. 

However, the research paper was highly critical of this model of appeal, too. ‘Hereby the WADA transfers the responsibility of resolving the flaws in the rules designed by WADA itself to the athlete. Setting up such a study and getting the desired result will take months at least. And even if an athlete does prove his innocence, this could already do major damage to a reputation (see the Froome case),’ the researchers wrote.

The same research centre, the Centre for Human Drug Research in Leiden, Netherlands,  last year produced a study that claimed there was no performance boost through the systemic use of EPO in a controlled hill climb competition. 

Limits and benefits

In addition to a criticism of the testing itself, the study also criticised the wider anabolic benefits of salbutamol for athletes. It claimed, ‘These issues, combined with the dubious assertion of its anabolic effect, leads us to conclude that the large effort involved in testing should be reconsidered.’

In an interview with Cyclist, Olivier Rabin, senior director of science and international relationships at WADA, defended WADA’s viewpoint that salbutamol has potentially anabolic properties.

‘There have been several studies, including animal models, showing that beta-2 agonists such as salbutamol can have an effect on muscle mass,’ he said.

Salbutamol has been shown repeatedly not to have an advantage within normally prescribed dosages. ‘We know that taking salbutamol inhalation of 800 micrograms per 12 hours is not performance enhancing,’ said Rabin. WADA believes, though, that higher dosages in different forms can bring about an advantage.  

‘We have an upper limit because we have multiple publications showing that systemic use of beta-2 antagonists [bronchodilators] including salbutamol can be performance enhancing – they can be anabolic agents if taken by systemic routes [meaning injection or ingestion of a pill, but not an inhaler],’ said Rabin of WADA’s position. 

A high content in urine would be indicative that there may have been systemic use rather than normal use of an inhaler, WADA believes.

However, the actual limit as set by WADA is determined by the maximum dosages as recommended by the pharmaceutical companies that produce the drug. Those are in place not to avoid people cheating, but to discourage asthma sufferers using too much salbutamol to manage asthma that requires a more powerful treatment. 

WADA falls back on these guidelines because while there is evidence that systemic use can have anabolic effects,  there have not been sufficient studies to demonstrate a specific dosage that would offer a performance gain.

The doubts cast on the possible performance enhancing benefits of salbutamol coupled with the possible testing errors will no doubt play an important part in Froome’s defence.

Defence

Froome’s salbutamol case is already proving to be one of the most complex in recent years. The AAF does not constitute a traditional doping violation, as salbutamol is a ‘Specified Substance’ not a purely ‘Prohibited Substance’. This is why he was not given a provisional suspension and has been able to continue racing.

While the results of a pharmacokinetic study would seem to clear Froome, the study from British Journal of Clinical Pharmacology claimed that based on their simulations a large number of trials could be needed to trigger the same result in any one individual, a process the researchers claimed would be ‘expensive and time consuming’.

Should Froome's defence prove successful, and rely on the ‘fundamental flaws’ in the testing system itself, it may have significant ramifications for those already sanctioned for exceeding the limit of salbutamol.

This includes the following:

  • Diego Ulissi of Team Lampre-Farnese Vini during the 2014 Giro d'Italia. He had recorded levels of 1,900ng/ml. He was initially issued a two year ban but this was reduced to nine months on appeal.
  • Alessandro Petacchi of Team Milram in 2007. He recorded levels of 1,352ng/ml. He was initially cleared by the Italian Cycling Federation, citing human error. WADA appealed this and he was banned for one year.
  • Alexandre Pliuschin, a Moldovan rider for Team Synergy Baku in 2014. Details are not available for the level of salbutamol he recorded, but he was suspended for six months.

The defence case does not appear to have a specified timeline, and so it’s unclear how long it may continue.

Should Froome’s defence case be unsuccessful, it is likely that the study will add to the strength of an appeal at the Court of Arbitration in Sport. 

Regardless of the eventual outcome, as we have seen with Tyson Fury’s case against UKAD’s positive test, given the high profile nature of the case, the legal battle could prove excessively expensive for WADA.