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
Bibliographic record
Abstract
Abstract 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".