Pharmacokinetics of Orally Administered GS-441524 in Dogs

Despite being FDA-approved for COVID-19, the clinical efficacy of remdesivir (Veklury(®)) remains contentious. We previously pointed out pharmacokinetic, pharmacodynamic and toxicology reasons for why its parent nucleoside GS-441524, is better suited for COVID-19 treatment. Here, we assess the oral...

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Autores principales: Yan, Victoria C., Pham, Cong-Dat, Yan, Matthew J., Yan, Alexander J., Khadka, Sunada, Arthur, Kenisha, Ackroyd, Jeffrey J., Georgiou, Dimitra K., Roon, Laura E., Bushman, Lane R., Anderson, Peter L., Li, Chun, Muller, Florian L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183013/
https://www.ncbi.nlm.nih.gov/pubmed/34100016
http://dx.doi.org/10.1101/2021.02.04.429674
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author Yan, Victoria C.
Pham, Cong-Dat
Yan, Matthew J.
Yan, Alexander J.
Khadka, Sunada
Arthur, Kenisha
Ackroyd, Jeffrey J.
Georgiou, Dimitra K.
Roon, Laura E.
Bushman, Lane R.
Anderson, Peter L.
Li, Chun
Muller, Florian L.
author_facet Yan, Victoria C.
Pham, Cong-Dat
Yan, Matthew J.
Yan, Alexander J.
Khadka, Sunada
Arthur, Kenisha
Ackroyd, Jeffrey J.
Georgiou, Dimitra K.
Roon, Laura E.
Bushman, Lane R.
Anderson, Peter L.
Li, Chun
Muller, Florian L.
author_sort Yan, Victoria C.
collection PubMed
description Despite being FDA-approved for COVID-19, the clinical efficacy of remdesivir (Veklury(®)) remains contentious. We previously pointed out pharmacokinetic, pharmacodynamic and toxicology reasons for why its parent nucleoside GS-441524, is better suited for COVID-19 treatment. Here, we assess the oral bioavailability of GS-441524 in beagle dogs and show that plasma concentrations ~24-fold higher than the EC(50) against SARS-CoV-2 are easily and safely sustained. These data support translation of GS-441524 as an oral agent for COVID-19.
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spelling pubmed-81830132021-06-08 Pharmacokinetics of Orally Administered GS-441524 in Dogs Yan, Victoria C. Pham, Cong-Dat Yan, Matthew J. Yan, Alexander J. Khadka, Sunada Arthur, Kenisha Ackroyd, Jeffrey J. Georgiou, Dimitra K. Roon, Laura E. Bushman, Lane R. Anderson, Peter L. Li, Chun Muller, Florian L. bioRxiv Article Despite being FDA-approved for COVID-19, the clinical efficacy of remdesivir (Veklury(®)) remains contentious. We previously pointed out pharmacokinetic, pharmacodynamic and toxicology reasons for why its parent nucleoside GS-441524, is better suited for COVID-19 treatment. Here, we assess the oral bioavailability of GS-441524 in beagle dogs and show that plasma concentrations ~24-fold higher than the EC(50) against SARS-CoV-2 are easily and safely sustained. These data support translation of GS-441524 as an oral agent for COVID-19. Cold Spring Harbor Laboratory 2021-05-31 /pmc/articles/PMC8183013/ /pubmed/34100016 http://dx.doi.org/10.1101/2021.02.04.429674 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Yan, Victoria C.
Pham, Cong-Dat
Yan, Matthew J.
Yan, Alexander J.
Khadka, Sunada
Arthur, Kenisha
Ackroyd, Jeffrey J.
Georgiou, Dimitra K.
Roon, Laura E.
Bushman, Lane R.
Anderson, Peter L.
Li, Chun
Muller, Florian L.
Pharmacokinetics of Orally Administered GS-441524 in Dogs
title Pharmacokinetics of Orally Administered GS-441524 in Dogs
title_full Pharmacokinetics of Orally Administered GS-441524 in Dogs
title_fullStr Pharmacokinetics of Orally Administered GS-441524 in Dogs
title_full_unstemmed Pharmacokinetics of Orally Administered GS-441524 in Dogs
title_short Pharmacokinetics of Orally Administered GS-441524 in Dogs
title_sort pharmacokinetics of orally administered gs-441524 in dogs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183013/
https://www.ncbi.nlm.nih.gov/pubmed/34100016
http://dx.doi.org/10.1101/2021.02.04.429674
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