Salbutamol metabolism. How to differentiate oral vs. inhaled administrations: looking outside the box

Salbutamol is one of the most used β2-adrenoceptor agonists by athletes for relieving bronchospasm and for prevention of exercise-induced-asthma. Inhalation is the preferred route of administration, but also an oral route is recommended, in particular for populations where inhalation presents practical problems (i.e. young children). Since salbutamol, similar to other β2-adrenoceptor agonists, produces an anabolic effect when administered by oral route, its use is approved by the World Anti-Doping Agency (WADA) only after inhaled administration. Previous studies have demonstrated that after oral administration, the majority of salbutamol is found in the urine either as the parent compound or as conjugated sulfate metabolite. On the contrary, no significant biotransformation occurs in the lungs, thus the percentage of salbutamol metabolite depends mainly on the percentage of the dose that is swallowed and absorbed from the gastrointestinal tract. The ratio between S(+) and R(-) of the unchanged salbutamol was proposed as marker of oral administration.