スポーツ医学およびドーピング研究ジャーナル

Urine Concentrations of Inhaled Salmeterol and its Metabolite a-Hydroxysalmeterol in Asthmatic and Non-Asthmatic Subjects

Abstract

Morten Hostrup, Anders Kalsen, Jimmi Elers, John Henninge, Peter Hemmersbach, Kim Dalhoff, Lars Petersen and Vibeke Backer

Salmeterol is a long-acting beta2-agonist, which is on the WADA prohibited list, but can be used by athletes in therapeutic doses by inhalation. The prohibited list, however, contains no urinary threshold for salmeterol, which gives athletes the opportunity to inhale unlimited doses of salmeterol. In doping controls, metabolites may be used as markers for misuse of substances. No studies have determined urine concentrations of α-hydroxysalmeterol, the metabolite of salmeterol. Furthermore, the metabolism and excretion of salmeterol may vary between asthmatics and nonasthmatics. We determined the serum and urinary concentrations of salmeterol and its metabolite α-hydroxysalmeterol after inhalation of 100 μg salmeterol in ten asthmatics and ten non-asthmatics. Blood samples were collected at baseline and ½, 1, 2, 3, 4 and 6 hours after the administration of salmeterol. Urine samples were collected at baseline and 4, 8 and 12 hours after administration. The urinary concentration of salmeterol following enzymatic hydrolysis of the glucuronide fraction was 0.38 ± 0.26 ngmL-1 in asthmatics and 0.38 ± 0.22 ngmL-1 in non-asthmatics, 4 hours after inhalation. The highest median serum concentration (Cmax) was 0.07 ± 0.03 ngmL-1 in asthmatics after 30 minutes (Tmax) and 0.06 ± 0.03 ngmL-1 in non-asthmatics. No statistical differences were found in Cmax or Tmax of salmeterol between asthmatics or non-asthmatics in neither the serum nor urine samples. The highest median urinary concentration of α-hydroxysalmeterol following enzymatic hydrolysis of the glucuronide fraction was 2.86 ± 1.75 ngmL-1 in asthmatics, 4 hours after inhalation of salmeterol. In non-asthmatics, it was 2.73 ± 2.08 ngmL-1. The asthmatics had a significantly (p<0.05) higher concentration after 12 hours compared with non-asthmatics. In doping control, α-hydroxysalmeterol may be a more suitable marker for excessive use of inhaled salmeterol, due to its higher concentration in urine.