Formoterol Concentrations in Blood and Urine: The WADA 2012 Regulations.
ABSTRACT PURPOSE: 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 with the WADA 2012 threshold for formoterol. METHODS: 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 non-asthmatic 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 World Anti-Doping Agency (WADA). Blood samples were collected at baseline, 30 min, 1, 2, 3, 4, and 6 hours after the first inhalation. Urine samples were collected at baseline, 0-4, 4-8, and 8-12 hours after the first inhalation. RESULTS: Median urine concentration, corrected for specific gravity, after the single-dose administration peaked during 0-4 hours after inhalation at a maximum of 7.4 ng*mL in asthmatic subjects and 7.9 ng*mL in healthy subjects. Median urine concentration after repeated doses peaked during 4-8 hours after inhalation of a total of 72 µg formoterol at a maximum of 16.8 ng*mL in healthy participants. The maximal individual concentration of 25.6 ng*mL was found after inhalation of a total of 72 µg formoterol. CONCLUSION: We found no significant differences in urinary and serum concentrations of formoterol between asthmatic and healthy subjects. We found high inter-individual variability in the concentrations in all groups. Our data support the WADA 2012 urinary threshold of 30 ng*mL formoterol as being an adverse analytical finding.