Formoterol concentrations in blood and urine: the World Anti-Doping Agency 2012 regulations

We examined urinary and serum concentrations of formoterol in asthmatic and healthy individuals after a single dose of 18 μg inhaled formoterol and after repeated inhaled doses in healthy individuals. Results were evaluated using the World Anti-Doping Agency (WADA) 2012 threshold for formoterol.

On the day of this open-label, crossover study, 10 asthmatic subjects who regularly used beta2-agonists and 10 healthy participants with no previous use of beta2-agonists received a single dose of 18 μg formoterol. Further, 10 nonasthmatic participants inhaled 18 μg formoterol every second hour until obtaining a total of 72 μg, which is twice the maximum daily dose (36 μg formoterol) permitted by the WADA. Blood samples were collected at baseline, 30 min, 1, 2, 3, 4, and 6 h after the first inhalation. Urine samples were collected at baseline, 0-4, 4-8, and 8-12 h after the first inhalation.

Median urine concentration, corrected for specific gravity, after the single-dose administration peaked during 0-4 h after inhalation at a maximum of 7.4 ng·mL(-1) in asthmatic subjects and 7.9 ng·mL(-1) in healthy subjects. Median urine concentration after repeated doses peaked during 4-8 h after inhalation of a total of 72 μg formoterol at a maximum of 16.8 ng·mL(-1) in healthy participants. The maximum individual concentration of 25.6 ng·mL(-1) was found after inhalation of a total of 72 μg formoterol.

We found no significant differences in urinary and serum concentrations of formoterol between asthmatic and healthy subjects. We found high interindividual variability in the concentrations in all groups. Our data support the WADA 2012 urinary threshold of 30 ng·mL(-1) formoterol as being an adverse analytical finding.