Pharmacokinetics of Orally Administered GS-441524 in Dogs-Reference-Cited by-同舟云学术

Pharmacokinetics of Orally Administered GS-441524 in Dogs

Published:2021-02-05 Issue: Volume: Page:
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Author:

Yan Victoria C.^ORCID,Pham Cong-Dat^ORCID,Yan Matthew J.,Yan Alexander J.,Khadka Sunada^ORCID,Arthur Kenisha,Ackroyd Jeffrey J.^ORCID,Georgiou Dimitra K.,Roon Laura E.,Bushman Lane R.,Anderson Peter L.,Li Chun^ORCID,Muller Florian L.^ORCID

Abstract

AbstractDespite 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 EC50 against SARS-CoV-2 are easily and safely sustained. These data support translation of GS-441524 as an oral agent for COVID-19.

Publisher

Cold Spring Harbor Laboratory

Reference36 articles.

1. Beigel JH , Tomashek KM , Dodd LE , Mehta AK , Zingman BS , Kalil AC , Hohmann E , Chu HY , Luetkemeyer A , Kline S , Lopez de Castilla D , Finberg RW , Dierberg K , Tapson V , Hsieh L , Patterson TF , Paredes R , Sweeney DA , Short WR , Touloumi G , Lye DC , Ohmagari N , Oh M , Ruiz-Palacios GM , Benfield T , Fätkenheuer G , Kortepeter MG , Atmar RL , Creech CB , Lundgren J , Babiker AG , Pett S , Neaton JD , Burgess TH , Bonnett T , Green M , Makowski M , Osinusi A , Nayak S , Lane HC . 2020. Remdesivir for the Treatment of Covid-19 — Final Report. N Engl J Med https://doi.org/10.1056/NEJMoa2007764.

2. WHO Solidarity Trial Consortium. 2020. Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results. N Engl J Med 1–15.

3. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial

4. Mcguigan C , Devine KG , O’oonnor TJ , Galpin SA , Jeffries DJ , Kinchington D. 1990. Synthesis and evaluation of some novel phosphoramidate derivatives of 3’-azido-3’-deoxythymidine (AZT) as anti-HIV compoundsAntiviral Chemistry & Chemotherapy.

5. Advantages of the Parent Nucleoside GS-441524 over Remdesivir for Covid-19 Treatment

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