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Model‐based meta‐analysis of salbutamol pharmacokinetics and practical implications for doping control

Salbutamol was included in the prohibited list of the World Anti‐Doping Agency (WADA) in 2004. Although systemic intake is banned, inhalation for asthma is permitted but with dosage restrictions. The WADA established a urinary concentration threshold to distinguish accordingly prohibited systemic se...

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Autores principales: Courlet, Perrine, Buclin, Thierry, Biollaz, Jérôme, Mazzoni, Irene, Rabin, Olivier, Guidi, Monia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007606/
https://www.ncbi.nlm.nih.gov/pubmed/35315251
http://dx.doi.org/10.1002/psp4.12773
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author Courlet, Perrine
Buclin, Thierry
Biollaz, Jérôme
Mazzoni, Irene
Rabin, Olivier
Guidi, Monia
author_facet Courlet, Perrine
Buclin, Thierry
Biollaz, Jérôme
Mazzoni, Irene
Rabin, Olivier
Guidi, Monia
author_sort Courlet, Perrine
collection PubMed
description Salbutamol was included in the prohibited list of the World Anti‐Doping Agency (WADA) in 2004. Although systemic intake is banned, inhalation for asthma is permitted but with dosage restrictions. The WADA established a urinary concentration threshold to distinguish accordingly prohibited systemic self‐administration from therapeutic prescription by inhalation. This study aimed at evaluating the ability of the WADA threshold to differentiate salbutamol therapeutic use from violation of antidoping rules. Concentration‐time profile of salbutamol in plasma and its excretion in urine was characterized through a model‐based meta‐analysis of individual and aggregate data collected after administration of a large range of doses following different modes of administration and under a variety of conditions. The developed model adequately fitted salbutamol plasma and urine concentration‐time profiles of the 13 selected studies. Model‐based simulations confirmed that a wide range of salbutamol urine concentrations might be measured after drug intake. Although violation of the WADA Code can be strongly suspected in individuals showing very high salbutamol urine concentrations, uncertainty remains for values close to the WADA threshold as they can be compatible with both permitted therapeutic use and violation. Although not entirely discriminant, the current WADA rule is globally supported by our appraisal. It could be further improved by a slight and reasonable adjustment of inhaled daily dosages allowed for therapeutic use. Our model might help antidoping experts in the evaluation of suspected doping cases through confronting the athlete's urine measurements with their allegations about salbutamol treatment.
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spelling pubmed-90076062022-04-15 Model‐based meta‐analysis of salbutamol pharmacokinetics and practical implications for doping control Courlet, Perrine Buclin, Thierry Biollaz, Jérôme Mazzoni, Irene Rabin, Olivier Guidi, Monia CPT Pharmacometrics Syst Pharmacol Research Salbutamol was included in the prohibited list of the World Anti‐Doping Agency (WADA) in 2004. Although systemic intake is banned, inhalation for asthma is permitted but with dosage restrictions. The WADA established a urinary concentration threshold to distinguish accordingly prohibited systemic self‐administration from therapeutic prescription by inhalation. This study aimed at evaluating the ability of the WADA threshold to differentiate salbutamol therapeutic use from violation of antidoping rules. Concentration‐time profile of salbutamol in plasma and its excretion in urine was characterized through a model‐based meta‐analysis of individual and aggregate data collected after administration of a large range of doses following different modes of administration and under a variety of conditions. The developed model adequately fitted salbutamol plasma and urine concentration‐time profiles of the 13 selected studies. Model‐based simulations confirmed that a wide range of salbutamol urine concentrations might be measured after drug intake. Although violation of the WADA Code can be strongly suspected in individuals showing very high salbutamol urine concentrations, uncertainty remains for values close to the WADA threshold as they can be compatible with both permitted therapeutic use and violation. Although not entirely discriminant, the current WADA rule is globally supported by our appraisal. It could be further improved by a slight and reasonable adjustment of inhaled daily dosages allowed for therapeutic use. Our model might help antidoping experts in the evaluation of suspected doping cases through confronting the athlete's urine measurements with their allegations about salbutamol treatment. John Wiley and Sons Inc. 2022-03-22 2022-04 /pmc/articles/PMC9007606/ /pubmed/35315251 http://dx.doi.org/10.1002/psp4.12773 Text en © 2022 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research
Courlet, Perrine
Buclin, Thierry
Biollaz, Jérôme
Mazzoni, Irene
Rabin, Olivier
Guidi, Monia
Model‐based meta‐analysis of salbutamol pharmacokinetics and practical implications for doping control
title Model‐based meta‐analysis of salbutamol pharmacokinetics and practical implications for doping control
title_full Model‐based meta‐analysis of salbutamol pharmacokinetics and practical implications for doping control
title_fullStr Model‐based meta‐analysis of salbutamol pharmacokinetics and practical implications for doping control
title_full_unstemmed Model‐based meta‐analysis of salbutamol pharmacokinetics and practical implications for doping control
title_short Model‐based meta‐analysis of salbutamol pharmacokinetics and practical implications for doping control
title_sort model‐based meta‐analysis of salbutamol pharmacokinetics and practical implications for doping control
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007606/
https://www.ncbi.nlm.nih.gov/pubmed/35315251
http://dx.doi.org/10.1002/psp4.12773
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