Does the urinary concentration of an inhaled beta 2 agonist always reflect the inhaled dose and method of administration?

Abstract

AbstractThe urinary threshold of 1000 ng/mL for salbutamol was established by the International Olympic Committee (IOC) in 2001 following a study that was not undertaken for that purpose. At least 25 athletes have exceeded this concentration and some after inhaling no more than the permitted daily maximum dose of 1600 μg. However, there is concern that some providing expert evidence and tribunal members hearing such cases are unaware of the occasional unpredictability of the pharmacokinetics of beta‐2 agonists. The World Anti‐Doping Agency's (WADA's) change from 1 March 2018 to allow correction of urinary specific gravity (SG) down to 1.020 for prohibited substances with a urinary threshold is a major advance and will assist in some instances. However, future cases are anticipated to occur when athletes unexpectedly exceed the urinary threshold for salbutamol after inhaling no more than the allowable dose and within WADA's stated time frame. They will then be required to appear before doping tribunals. The rapidity by which salbutamol is inhaled can influence the resultant urinary concentration and is yet to be addressed adequately in WADA's 2019 Prohibited List. The list's recommended pharmacokinetic study fails to replicate the circumstances that prevailed when the athlete was competing and the adverse analytical finding (AAF) occurred. Tribunals, and experts who advise them, need to be cognizant that the urinary concentration of salbutamol does not invariably reflect the inhaled dose and that a high urinary salbutamol concentration is not always ipso facto evidence of super‐dosing with inhaled salbutamol.