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Pharmacokinetics of Orally Administered GS-441524 in Dogs

View ORCID ProfileVictoria C. Yan, View ORCID ProfileSunada Khadka, Kenisha Arthur, View ORCID ProfileCong-Dat Pham, Matthew J. Yan, Alexander J. Yan, View ORCID ProfileJeffrey J. Ackroyd, Dimitra K. Georgiou, View ORCID ProfileFlorian L. Muller
doi: https://doi.org/10.1101/2021.02.04.429674
Victoria C. Yan
1Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX, USA
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  • For correspondence: victoriacyanide@gmail.com
Sunada Khadka
1Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX, USA
2Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Kenisha Arthur
1Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Cong-Dat Pham
1Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Matthew J. Yan
3Department of Chemistry, Boston College, Chestnut Hill, MA, USA
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Alexander J. Yan
3Department of Chemistry, Boston College, Chestnut Hill, MA, USA
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Jeffrey J. Ackroyd
1Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Dimitra K. Georgiou
1Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Florian L. Muller
1Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX, USA
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  • ORCID record for Florian L. Muller
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Abstract

Despite being FDA-approved for COVID-19, the clinical efficacy of remdesivir (Veklury®) remains contentious. We previously described the pharmacokinetic, pharmacodynamic and toxicological rationales on the greater suitability of its parent nucleoside, GS-441524, for COVID-19 treatment. Here, we assess the oral bioavailability of GS-441524 in beagle dogs and show that plasma concentrations approximately 24-fold higher than the EC50 against SARS-CoV-2 are easily and safely sustained. These data support translation of GS-441524 as an oral agent for COVID-19.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Updated author list to accurately reflect contributions.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted February 22, 2021.
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Pharmacokinetics of Orally Administered GS-441524 in Dogs
Victoria C. Yan, Sunada Khadka, Kenisha Arthur, Cong-Dat Pham, Matthew J. Yan, Alexander J. Yan, Jeffrey J. Ackroyd, Dimitra K. Georgiou, Florian L. Muller
bioRxiv 2021.02.04.429674; doi: https://doi.org/10.1101/2021.02.04.429674
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Pharmacokinetics of Orally Administered GS-441524 in Dogs
Victoria C. Yan, Sunada Khadka, Kenisha Arthur, Cong-Dat Pham, Matthew J. Yan, Alexander J. Yan, Jeffrey J. Ackroyd, Dimitra K. Georgiou, Florian L. Muller
bioRxiv 2021.02.04.429674; doi: https://doi.org/10.1101/2021.02.04.429674

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