TY - JOUR

T1 - Urine concentrations of vilanterol and its metabolites, GSK932009 and GW630200, after inhalation of therapeutic and supratherapeutic doses

AU - Østergaard, Martin

AU - Jessen, Søren

AU - Hansen, Erik Søren Halvard

AU - Backer, Vibeke

AU - Panchal, Tina

AU - Baldwin, Sandra

AU - Daley-Yates, Peter

AU - Hostrup, Morten

N1 - This article is protected by copyright. All rights reserved.

PY - 2023

Y1 - 2023

N2 - The 2023 Prohibited List issued by the World Anti-Doping Agency (WADA) permits athletes to inhale beta2-agonist vilanterol at a standard dose of 25 μg daily. However, given limited data on urine pharmacokinetics, vilanterol has no urinary threshold or decision limit to discriminate therapeutic from supratherapeutic use. We investigated urine concentrations of vilanterol and its main metabolites GSK932009 and GW630200 over 0-72 hours following inhalation of therapeutic (25 μg) or supratherapeutic (100 μg) doses and repeat-dose administration for 7 days of 25 or 100 μg×day-1 in 25 trained men and women. Vilanterol administration was followed by 1 hour of exercise. GW630200 urine concentrations were low and insufficient for threshold purposes, and while GSK932009 had higher urine concentrations, it could not discriminate between therapeutic and supratherapeutic use. Mean (range) maximum urine concentrations of parent vilanterol were 1.2(0.2-4.1) and 6.2(1.4-14.3) ng×mL-1 for single-dose 25 and 100 μg vilanterol, respectively, and 2.0(0.3-4.8) and 22.4(6.4-42.1) ng×mL-1 for repeat-dose 25 and 100 μg×day-1 vilanterol. In 333 samples collected 6 hours post-administration and considering WADA TD2022DL, a 3.1 ng×mL-1 vilanterol cut-off showed a 30% sensitivity in detecting supratherapeutic use at 100 μg versus therapeutic use at 25 μg. Considering inter- and intra-individual variability and guard bands in doping analysis, a 6 ng×mL-1 decision limit, which could be shifted upwards in samples with specific gravity >1.018, appears sufficiently high to minimize risk of samples exceeding the decision limit after therapeutic use of vilanterol, while demonstrating the ability to detect supratherapeutic use at 100 μg.

AB - The 2023 Prohibited List issued by the World Anti-Doping Agency (WADA) permits athletes to inhale beta2-agonist vilanterol at a standard dose of 25 μg daily. However, given limited data on urine pharmacokinetics, vilanterol has no urinary threshold or decision limit to discriminate therapeutic from supratherapeutic use. We investigated urine concentrations of vilanterol and its main metabolites GSK932009 and GW630200 over 0-72 hours following inhalation of therapeutic (25 μg) or supratherapeutic (100 μg) doses and repeat-dose administration for 7 days of 25 or 100 μg×day-1 in 25 trained men and women. Vilanterol administration was followed by 1 hour of exercise. GW630200 urine concentrations were low and insufficient for threshold purposes, and while GSK932009 had higher urine concentrations, it could not discriminate between therapeutic and supratherapeutic use. Mean (range) maximum urine concentrations of parent vilanterol were 1.2(0.2-4.1) and 6.2(1.4-14.3) ng×mL-1 for single-dose 25 and 100 μg vilanterol, respectively, and 2.0(0.3-4.8) and 22.4(6.4-42.1) ng×mL-1 for repeat-dose 25 and 100 μg×day-1 vilanterol. In 333 samples collected 6 hours post-administration and considering WADA TD2022DL, a 3.1 ng×mL-1 vilanterol cut-off showed a 30% sensitivity in detecting supratherapeutic use at 100 μg versus therapeutic use at 25 μg. Considering inter- and intra-individual variability and guard bands in doping analysis, a 6 ng×mL-1 decision limit, which could be shifted upwards in samples with specific gravity >1.018, appears sufficiently high to minimize risk of samples exceeding the decision limit after therapeutic use of vilanterol, while demonstrating the ability to detect supratherapeutic use at 100 μg.

KW - Faculty of Science

KW - Doping control

KW - Beta2-agonist

KW - Relvar

KW - Vilanterol

KW - Pharmacokinetics

U2 - 10.1002/dta.3437

DO - 10.1002/dta.3437

M3 - Journal article

C2 - 36610030

VL - 15

SP - 516

EP - 528

JO - Drug Testing and Analysis

JF - Drug Testing and Analysis

SN - 1942-7603

IS - 5

ER -