Urine concentrations of vilanterol and its metabolites, GSK932009 and GW630200, after inhalation of therapeutic and supratherapeutic doses
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Urine concentrations of vilanterol and its metabolites, GSK932009 and GW630200, after inhalation of therapeutic and supratherapeutic doses. / Østergaard, Martin; Jessen, Søren; Hansen, Erik Søren Halvard; Backer, Vibeke; Panchal, Tina; Baldwin, Sandra; Daley-Yates, Peter; Hostrup, Morten.
In: Drug Testing and Analysis, Vol. 15, No. 5, 2023, p. 516-528.Research output: Contribution to journal › Journal article › Research › peer-review
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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 -
ID: 332182856