The influence of exercise and dehydration on the urine concentrations of salbutamol after inhaled administration of 1600 µg salbutamol as a single dose in relation to doping analysis

Abstract

The present study investigated the influence of exercise and dehydration on the urine concentrations of salbutamol after inhalation of that maximal permitted (1600 µg) on the 2015 World Anti-Doping Agency (WADA) prohibited list. Thirteen healthy males participated in the study. Urine concentrations of salbutamol were measured during three conditions: exercise (EX), exercise+dehydration (EXD), and rest (R). Exercise consisted of 75 min cycling at 60% of VO2max and a 20-km time-trial. Fluid intake was 2300, 270, and 1100 mL during EX, EXD, and R, respectively. Urine samples of salbutamol were collected 0-24 h after drug administration. Adjustment of urine concentrations of salbutamol to a specific gravity (USG) of 1.020 g/mL was compared with no adjustment. The 2015 WADA decision limit (1200 ng/mL) for salbutamol was exceeded in 23, 31, and 10% of the urine samples during EX, EXD, and R, respectively, when unadjusted for USG. When adjusted for USG, the corresponding percentages fell to 21, 15, and 8%. During EXD, mean urine concentrations of salbutamol exceeded (1325±599 ng/mL) the decision limit 4 h after administration when unadjusted for USG. Serum salbutamol Cmax was lower (P<0.01) for R(3.0±0.7 ng/mL) than EX(3.8±0.8 ng/mL) and EXD(3.6±0.8 ng/mL). AUC was lower for R (14.1±2.8 ng/mL·∙h) than EX (16.9±2.9 ng/mL·∙h)(P<0.01) and EXD (16.1±3.2 ng/mL·∙h)(P<0.05). In conclusion, exercise and dehydration affect urine concentrations of salbutamol and increase the risk of Adverse Analytical Findings in samples collected after inhalation of that maximal permitted (1600 µg) for salbutamol. This should be taken into account when evaluating doping cases of salbutamol. Copyright © 2015 John Wiley & Sons, Ltd.

Influence of exercise in normal and hot ambient conditions on the pharmacokinetics of inhaled terbutaline in trained men

“…Although several studies have investigated urine concentrations of salbutamol with respect to doping analysis (Ventura et al., ; Pichon et al., ; Sporer et al., ; Haase et al., ), pharmacokinetic data on terbutaline are insufficient. Elers et al.…”

“…Usually an athlete, who uses beta 2 ‐agonist, will inhale the active substance before competition and training as prophylaxis against bronchoconstriction (Arie, ; Price et al., ). In previous studies, it has been shown that exercise modifies pharmacokinetics of drugs (Kamimori et al., ; Khazaeinia et al., ), including beta 2 ‐agonists (Schmekel et al., ; Haase et al., ). Furthermore, exercise‐induced sweating affects hydration status.…”

“…Furthermore, exercise‐induced sweating affects hydration status. Dehydration may concentrate urine and result in higher concentrations of beta 2 ‐agonists in urine samples (Dickinson et al., ; Haase et al., ). It has been proposed that the urine‐specific gravity (USG) can be used to adjust urine concentrations of samples that are concentrated or diluted in doping control (Sporer et al., ; Hostrup et al., ; Haase et al., ).…”

The enigma of inhaled salbutamol and sport: unresolved after 45 years

“…[27,[32][33][34] Significantly, a Danish group reported a subject exceeding the 1000 ng/mL threshold after only 800 μg of inhaled salbutamol but the concentration fell to only 661 ng/mL if the urinary SG was corrected to 1.020. salbutamol, in that urine and hence demands a TUE for that substance.…”

Terbutaline: level the playing field for inhaled β2-agonists by introducing a dosing and urine threshold

“…There is no doubt that urinary thresholds and decision limits for salbutamol and formoterol introduced by WADA is an innovative way to avoid excessive use by athletes and to lessen the economic burdens associated with TUE applications. Despite this, urine thresholds can be problematic and athletes should be aware that severe dehydration during and after exercise have been shown to increase the risk of exceeding the urine threshold for salbutamol following inhalation 6 7. With terbutaline, the lack of a urinary threshold and decision limit means that an athlete can administer either oral or supratherapeutic inhaled doses with impunity as long as there is a current TUE.…”