title: Medical and pharmacological approach to adjust the salbutamol anti-doping policy in athletes.
abstract: BACKGROUND
  Salbutamol abuse detection by athletes is based on a urinary upper threshold defined by the World Anti-Doping Agency (WADA). However, this threshold was determined in healthy, untrained individuals and after a dose of salbutamol inhaled that might not really mirror the condition of asthmatic athletes and the experts's guidelines for asthma management. We aimed to revise this threshold in accordance with recommended clinical practice (that appear to be different from the actual WADA recommendation) and in exercise conditions.
  
  
  METHODS
  For the present open-label design study, we included 12 trained male cyclists (20 to 40 y/o) with asthma. Differently from the previous pharmacokinetic study supporting the actual salbutamol urinary upper threshold, we decided to administer a close to recommended clinical practice daily dose of 3x200 μg.d(-1) inhaled salbutamol (instead of 1600 μg.d(-1) as authorized by the anti-doping policy). Urine salbutamol concentration was quantified by liquid chromatography-tandem ion trap mass spectrometry and corrected for urine density, at rest and after a 90-min cycling effort at 70-80 % of the maximal aerobic power.
  
  
  RESULTS
  The maximum urine salbutamol concentration value peaked after the cycling effort and was 510 ng.mL(-1). That is twice lower than the actual WADA threshold to sanction salbutamol abuse, this "legal" threshold being based on pharmacokinetic data after a daily dose that is 8 fold the total dose sequentially administrated in our study. Considering its 95 % confidence interval, this threshold value could be more stringent.
  
  
  CONCLUSIONS
  By using conditions in accordance with the experts' clinical and safety guidelines for asthma management in athletes undergoing an intense exercise bout, our study suggests that the urine salbutamol concentration threshold could be lowered to redefine the rule supporting the decision to sanction an athlete for salbutamol abuse.
authors.affiliation: Respiratory Function Exploration and Sport Medicine Department, Larrey Hospital, 24 Chemin de Pouvourville, TSA 30030, 31059, Toulouse Cedex 9, France. pillard.f@chu-toulouse.fr.|Exercise Physiology Department, Medical School, Paul Sabatier University, Toulouse, France. pillard.f@chu-toulouse.fr.|INSERM, U858-Adipolab Unit, Institute of Molecular Medicine, Toulouse, France. pillard.f@chu-toulouse.fr.
authors.forename: Fabien
authors.initials: F
authors.lastname: Pillard
authors.affiliation: Pharmacokinetic and Toxicologic Laboratory, Institute of Biology, Purpan Hospital, Toulouse, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Lavit
authors.affiliation: Epidemiology Department, Medical School, Paul Sabatier University, Toulouse, France.
authors.forename: Valérie Lauwers
authors.initials: VL
authors.lastname: Cances
authors.affiliation: Respiratory Function Exploration and Sport Medicine Department, Larrey Hospital, 24 Chemin de Pouvourville, TSA 30030, 31059, Toulouse Cedex 9, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Rami
authors.affiliation: Pharmacokinetic and Toxicologic Laboratory, Institute of Biology, Purpan Hospital, Toulouse, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Houin
authors.affiliation: Department of Respiratory Diseases, Larrey Hospital, Toulouse, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Didier
authors.affiliation: Respiratory Function Exploration and Sport Medicine Department, Larrey Hospital, 24 Chemin de Pouvourville, TSA 30030, 31059, Toulouse Cedex 9, France.|Exercise Physiology Department, Medical School, Paul Sabatier University, Toulouse, France.|INSERM, U858-Adipolab Unit, Institute of Molecular Medicine, Toulouse, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rivière
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000652:urine; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000652:urine; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D001642:Bicycling; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000652:urine; D002853:Chromatography, Liquid; D004300:Doping in Sports / Q000331:legislation & jurisprudence*; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D011050:Policy Making; D015813:Substance Abuse Detection / Q000379:methods; D053719:Tandem Mass Spectrometry; D016896:Treatment Outcome; D016482:Urinalysis; D055815:Young Adult
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D000420:Albuterol