Salbutamol Data

Code: T20M04JB

Salbutamol is a fast- and short-acting β2-adrenergic receptor agonist, indicated for the treatment of asthma attacks and the prevention of exercise-induced bronchospasm. It is one of the medications most frequently used by athletes, generally for its bronchodilating effect, but also sometimes for its ergogenic properties. Some evidence indicates a positive effect of systemic salbutamol on physical performance while no significant effect is demonstrated for inhaled salbutamol [1-3]. After oral administration, salbutamol undergoes a significant first-pass metabolism. It is predominantly metabolized by SULT1A3, expressed primarily in the intestine [4], into an inactive sulfoconjugated metabolite [5]. After oral intake, a roughly one third of the dose is excreted in the urine unchanged (free), and one half as sulfoconjugate [5]. Another small fraction (<3%) is found as glucuroconjugated metabolite [6]. Conversely, salbutamol is not extensively metabolized in the lungs [7] and after inhalation, the fraction of the dose actually absorbed in the circulation through this route is mainly eliminated in the urine as the free form, while a low proportion of sulfoconjugate and a negligible fraction of glucuroconjugated metabolite are excreted [6]. However, the remaining fraction administered by inhalation settles along the oral cavity and the throat or is carried back from the tracheobronchial by mucociliary clearance, thus resulting into ingestion and gastrointestinal absorption.

Main findings

The objective of this work was to evaluate the capacity of the current WADA approach to differentiate salbutamol therapeutic use from violation. A population PK analysis including both individual and 
aggregate data from the literature was developed using up-to-date MBMAtechniquesto characterize salbutamol plasma and urine PK profiles after inhalation or oral administration, under various dosing 
regimens and conditions.

In conclusion, although not entirely satisfactory, the current WADA rules regarding the definition of AAFs related to salbutamol could be globally maintained, and possibly improved by a slight and 
reasonable modification of inhalation dosages allowed in therapeutic exemption. Moreover, the use of such a model might help WADA experts in their evaluation of individual AAFs through the 
confrontation of the athlete’s allegation about treatment intake.