The Pharmacokinetic Profile of Inhaled and Oral Salbutamol in Elite Athletes With Asthma and Nonasthmatic Subjects

Elers, Jimmi; Pedersen, Lars; Henninge, John; Hemmersbach, Peter; Dalhoff, Kim; Backer, Vibeke

doi:10.1097/jsm.0b013e31823513e1

Cited by 28 publications

(48 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[12] Unlike Elers et al, [19] our previous work found this variability only modestly improved by correction for dilution. This was done to avoid any random error associated with measurement in urine as these are notoriously variable and correction for dilution remains problematic.…”

Section: Discussioncontrasting

confidence: 55%

SULT 1A3 single‐nucleotide polymorphism and the single dose pharmacokinetics of inhaled salbutamol enantiomers: Are some athletes at risk of higher urine levels?

Jacobson

Yee

Wood‐Baker

et al. 2014

Drug Testing and Analysis

View full text Add to dashboard Cite

The study was designed to investigate the effect of a common genetic variation of the main salbutamol metabolizing enzyme SULT1A3 (single nucleotide polymorphism 105A>G, rs1975350) on the stereoselective pharmacokinetics of salbutamol. Subjects were administered a 400 µg dose of inhaled salbutamol via a large volume spacer and blood samples were collected over 4 h. Plasma levels of (R)- and (S)-salbutamol were determined by an enantioselective liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. Twenty-five subjects with asthma were recruited and underwent SULT1A3 genotyping, from which four SNP homozygote (GG) subjects and nine wild-type (AA) subjects were selected to participated in the pharmacokinetic investigation. There were no differences in pharmacokinetic parameters (t1/2 , Cmax , AUC0-4h ) between SNP and wild-type genotypes for either the R- or S-enantiomer. Observed Cmax of R- and S-salbutamol [mean (SD)] was 0.64 (0.30) ng/mL and 1.32 (0.98) ng/mL, respectively. The mean t1/2 of R- and S-salbutamol was estimated at 2.94 (1.17) h and 7.86 (6.14) h respectively. The AUC0-4h of R- and S-salbutamol was 14.0 (6.8) and 38.3 (19.5) ng/mL.h respectively. In conclusion, the common SULT1A3 SNP 105A>G is not an important determinant of salbutamol enantiomer pharmacokinetics under normal clinical use and does not place some individuals at greater risk of accumulation in the body.

show abstract

Section: Discussioncontrasting

confidence: 55%

SULT 1A3 single‐nucleotide polymorphism and the single dose pharmacokinetics of inhaled salbutamol enantiomers: Are some athletes at risk of higher urine levels?

Jacobson

Yee

Wood‐Baker

et al. 2014

Drug Testing and Analysis

View full text Add to dashboard Cite

show abstract

“…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 . Sporer et al .…”

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Previous research has attempted to examine the excretion of salbutamol administered by diferent routes including oral and inhaled [16,17] and across a range of acute doses from 200 μg and 800 μg [18] and repeated doses over several hours [19]. he current study is the irst to examine the urinary excretion of an acute, high dose in comparison with an intermediate dose following intermittent running in soccer players.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Inhaled Salbutamol on Repeated Sprint Ability in Pre- Fatigued Soccer Players

J¹,

M²

2015

J Sports Med Doping Stud

View full text Add to dashboard Cite

John et al., J Sports Med Doping Stud 2015, 5:S2 http://dx.doi.org/10.4172/2161 Research Article Open Access AbstractObjectives: Investigate the ergogenic effect of inhaling up to 1600 µg of salbutamol on intermittent running performance in pre-fatigued soccer players. Methods:In a single blind randomised repeated measures design seven male and six female soccer players volunteered to participant. All participants were regularly playing competitive soccer and had no history of asthma. Following familiarisation sessions participants visited the exercise physiology laboratory on three occasions to complete an intermittent running protocol followed by twelve 17.5 m sprints. Prior to each trial participants inhaled either: placebo, 800 µg inhaled salbutamol (SAL800) or 1600 µg inhaled salbutamol (SAL1600). Following completion of the sprints a sample from the irst urine passed was analysed for salbutamol concentration. A repeated measures ANOVA was used to compare the mean sprint time, maximal sprint power, peak blood lactate post sprints and post sprint salbutamol urine concentration between conditions.Results: Mean sprint time, maximum power, maximum velocity, peak HR and peak blood lactate during the 17.5 m sprints were not signiicantly different between treatments in soccer players. There was no signiicant difference between male and female players in urine drug concentration following SAL800 (mean + SD; 201.47 + 294.47 ng.ml -1 vs. 180.2 + 102.15 ng.ml -1 ) or SAL1600 (739.24 + 549.21 ng.ml -1 vs. 879.58 + 633.14 ng.ml -1 ). Three players urine drug concentrations were above the WADA decision limit set at 1200 ng.ml -1 . Conclusions:Inhaling up to 1600 µg inhaled salbutamol did not signiicantly improve repeated sprint performance. However, inhalation of 1600 µg may result in a urine concentration above the current WADA upper limit and decision limit leading to a positive test. Athletes should ensure they use inhaled salbutamol at therapeutic doses to avoid the risk of breaching the WADA decision limit.

show abstract

The Pharmacokinetic Profile of Inhaled and Oral Salbutamol in Elite Athletes With Asthma and Nonasthmatic Subjects

Abstract: We found no significant difference in pharmacokinetic profile of inhaled and oral salbutamol between elite athletes with asthma and nonasthmatic subjects. Our results indicate that urine salbutamol concentrations should be corrected for urine specific gravity when evaluating doping cases.

Cited by 28 publications

References 16 publications

SULT 1A3 single‐nucleotide polymorphism and the single dose pharmacokinetics of inhaled salbutamol enantiomers: Are some athletes at risk of higher urine levels?

SULT 1A3 single‐nucleotide polymorphism and the single dose pharmacokinetics of inhaled salbutamol enantiomers: Are some athletes at risk of higher urine levels?

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 Impact of Inhaled Salbutamol on Repeated Sprint Ability in Pre- Fatigued Soccer Players

Contact Info

Product

Resources

About