Urine Concentrations of Repetitive Doses of Inhaled Salbutamol

Abstract

We examined blood and urine concentrations of repetitive doses of inhaled salbutamol in relation to the existing cut-off value used in routine doping control. We compared the concentrations in asthmatics with regular use of beta2-agonists prior to study and healthy controls with no previous use of beta2-agonists. We enrolled 10 asthmatics and 10 controls in an open-label study in which subjects inhaled repetitive doses of 400 microgram salbutamol every second hour (total 1600 microgram), which is the permitted daily dose by the World Anti-Doping Agency (WADA). Blood samples were collected at baseline, 30 min, 1, 2, 3, 4, and 6 h after the first inhalations. Urine samples were collected at baseline, 0-4 h, 4-8 h, and 8-12 h after the first inhalations. Median urine concentrations peaked in the period 4-8 h after the first inhalations in the asthmatics and between 8-12 h in controls and the median ranged from 268 to 611 ng×mL (-1). No samples exceeded the WADA threshold value of 1000 ng×mL (-1) when corrected for the urine specific gravity. When not corrected one sample exceeded the cut-off value with urine concentration of 1082 ng×mL (-1). In conclusion we found no differences in blood and urine concentrations between asthmatic and healthy subjects. We found high variability in urine concentrations between subjects in both groups. The variability between subjects was still present after the samples were corrected for urine specific gravity.

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

“…A limitation of the present study was that the subjects were not elite athletes or asthmatics. Nonetheless, previous pharmacokinetic studies found no differences in the urine concentrations of salbutamol between athletic and non‐athletic subjects or between asthmatics and non‐asthmatics after oral and inhaled administration . Therefore, the present findings may be applicable for WADA.…”

“…While the administered dose of 1600 µg salbutamol as a single inhaled dose used in the present study, exceeds that considered as normal therapeutic treatment, athletes are often medically advised to inhale the amount that is needed to relieve asthma symptoms (pro re nata) . Athletes using salbutamol may inhale repetitive doses prior to a warm‐up and again before and after competition . Indeed, doping case reports have shown that athletes inhale salbutamol repetitively during competition .…”

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

“…Therefore, it seems unclear why urine samples of beta 2 ‐agonists are unadjusted for USG in doping analysis. Recent studies have reported urine concentrations of salbutamol near the decision limit of 1200 ng/mL when unadjusted for USG, even after inhalation of salbutamol in therapeutic doses within the current threshold . As such, Elers et al .…”

Annual banned‐substance review: analytical approaches in human sports drug testing

“…Using a triple quadrupole mass spectrometer, an LOQ of 24 ng/ml was accomplished and the fitness‐for‐purpose was shown by applying the established methodology to inter‐laboratory ring test samples. The rationale of the urinary threshold of 1000 ng/ml of salbutamol was re‐assessed by analyzing urine samples collected after repetitive dosing of inhaled salbutamol by asthmatic and non‐asthmatic persons up to the allowed daily amount of 1600 µg . After correction of measured urinary concentrations concerning their specific gravity, no sample exceeded the permitted threshold in either group, supporting the validity of the established limit.…”