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Pharmacokinetics of salmeterol and its main metabolite α‐hydroxysalmeterol after acute and chronic dry powder inhalation in exercising endurance‐trained men: Implications for doping control
Author(s) -
Jessen Søren,
Becker Victoria,
Rzeppa Sebastian,
Backer Vibeke,
Bengtsen Kasper Høtoft,
Hullstein Ingunn,
Dehnes Yvette,
Hostrup Morten
Publication year - 2021
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.2978
Subject(s) - salmeterol , formoterol , inhalation , salbutamol , urine , bronchodilator , medicine , pharmacology , anesthesia , chemistry , asthma , budesonide
As of 2020, use of beta 2 ‐agonist salmeterol is restricted by the World Anti‐Doping Agency (WADA) and is only permitted by inhalation at therapeutic doses not exceeding 200 μg in 24 h. In contrast to beta 2 ‐agonists salbutamol and formoterol, WADA has not established a urine threshold for salmeterol despite its muscle hypertrophic actions observed in animals. Herein, we investigated plasma (0–4 h) and urine (0–24 h) concentrations (by ultra‐high‐performance liquid chromatography–tandem mass spectrometry [UHPLC–MS/MS]) of salmeterol and α‐hydroxysalmeterol after dry powder inhalation at supratherapeutic (400 μg) and high therapeutic (200 μg) doses, and after seven consecutive days of therapeutic inhalation (200 μg × day −1 ) in 11 healthy endurance‐trained men. During each trial, participants inhaled salmeterol before 1½ h moderate‐intensity cycling. Mean ± SD maximum urine concentrations of salmeterol unadjusted for specific gravity reached 4.0 ± 1.6, 2.1 ± 1.5, and 2.2 ± 1.1 ng × ml −1 for 400 μg, 200 μg, and seven consecutive days of 200 μg, respectively, with corresponding maximum urine concentrations of α‐hydroxysalmeterol being 11.6 ± 6.1, 5.7 ± 4.6, and 6.5 ± 2.6 ng × ml −1 . Within the relevant window for doping control (first 6 h post‐inhalation), the present data (119 samples), along with 64 biobank urine samples, showed that a combined salmeterol and α‐hydroxysalmeterol urine threshold with equal cut‐offs of 3.3 ng × ml −1 was superior to a salmeterol‐only threshold to discriminate therapeutic (200 μg) from supratherapeutic use (400 μg) with a sensitivity of 24% with 0% false positives when applying the WADA technical document (TD2019DL.v2) method of specific gravity adjustment. Thus, a combination of urine salmeterol and α‐hydroxysalmeterol concentrations may be suitable for discriminating between therapeutic and supratherapeutic prohibited inhalation of salmeterol.