Urine concentrations of oral salbutamol in samples collected after intense exercise in endurance athletes

Hostrup, Morten; Kalsen, Anders; Auchenberg, Michael; Rzeppa, Sebastian; Hemmersbach, Peter; Bangsbo, Jens; Backer, Vibeke

doi:10.1002/dta.1568

Cited by 19 publications

(35 citation statements)

References 19 publications

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“…Exercise may also compromise blood flow to the splanchnic region and reduce gastro‐intestinal uptake of the part of the drug that is swallowed during inhalation (up to 80% for inhaled salbutamol) . Furthermore, exercise‐induced sweat loss concentrates the urine, thus leading to a higher urine concentration of beta 2 ‐agonists . Adjustment of urine samples of beta 2 ‐agonists to a USG of 1.020 g/mL has been shown to be a way to correct for hydration status and to change the outcome from false negative to true positive doping test results and false positive to true negative .…”

Section: Introductionmentioning

confidence: 99%

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

Haase

Backer

Kalsen

et al. 2015

Drug Testing and Analysis

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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.

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Section: Introductionmentioning

confidence: 99%

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

Haase

Backer

Kalsen

et al. 2015

Drug Testing and Analysis

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“…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., ). Adjustment of urine samples of salbutamol for USG has thus been shown to reduce the number of false‐positive AAFs after inhalation of the maximally allowed daily dose of 1600 μg for salbutamol (Haase et al., ).…”

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confidence: 99%

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

Kreiberg

Becker

Jessen

et al. 2016

Scandinavian Med Sci Sports

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This study investigated the pharmacokinetics of inhaled terbutaline at rest and after exercise in normal and hot ambient conditions with respect to doping analysis. Thirteen trained young men participated in the study. Urine and blood samples were collected after inhalation of 4 mg terbutaline during three trials: exercise in hot ambient conditions (30-35 °C) (EXH), exercise in normal ambient conditions (20-25 °C) (EX), and rest (20-25 °C) (R). Exercise consisted of 130 min at various intensities. Adjustment of urine concentrations of terbutaline to a specific gravity (USG) of 1.02 g/mL was compared with no adjustment. Area under the serum concentration-time curve within the first 6 h was higher for EX (27 ± 3 ng/mL/h) (P ≤ 0.01) and EXH (25 ± 4 ng/mL/h) (P ≤ 0.05) than for R (20 ± 3 ng/mL/h). When unadjusted for USG, urine concentrations of terbutaline after 4 h were different in the order EXH > EX > R (P ≤ 0.01). When unadjusted for USG, urine concentrations of terbutaline were 299 ± 151 ng/mL higher (P ≤ 0.001) after 4 h compared with adjusted concentrations in EXH. Excretion rate of terbutaline was higher (P ≤ 0.001) for EX than for EXH and R within the first 0-1½ h. In conclusion, EXHs results in higher urine concentrations of terbutaline. This should be considered when evaluating doping cases of terbutaline.

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“…[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.…”

Section: Pharmacokinetic Studymentioning

confidence: 99%

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

Fitch

2017

Drug Testing and Analysis

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During the past 45 years, there have been more changes on the World Anti-Doping Agency's (WADA) Prohibited List (the List) to the status of inhaled salbutamol than any other substance. With 658 athletes, 6.1% of all participating athletes approved to inhale salbutamol at the 2008 Beijing Games, it is one of the medications used most frequently by Olympic athletes. Nevertheless, since the 2008 Games, WADA has made numerous changes to inhaled salbutamol on the List including prohibiting its use, then a year later permitting it without prior notification and recommending a pharmacokinetic study if an athlete exceeds the urinary threshold of 1000 ng/mL. Recently, an elite athlete undertook two pharmacokinetic studies and the results have raised several questions. These include whether WADA should continue to permit nebulized salbutamol as an acceptable method of inhalation and there is some justification for nebulized salbutamol to be prohibited in sport. Another question is whether the modified advisory on salbutamol in the 2017 List appropriately informs athletes of the risks of exceeding the urinary threshold and the recent changes may not inform athletes optimally. Finally, concern is expressed at the persistent failure of WADA to apply a correction down to a specific gravity of 1.020 when an exogenous substance is identified in the urine of a dehydrated athlete. It is recommended that this should be implemented. Copyright © 2017 John Wiley & Sons, Ltd.

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Urine concentrations of oral salbutamol in samples collected after intense exercise in endurance athletes

Cited by 19 publications

References 19 publications

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

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

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

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

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