Pharmacokinetics of Orally Administered GS-441524 in Dogs.
Pharmacokinetics of Orally Administered GS-441524 in Dogs.
复制标题
狗口服 GS-441524 的药代动力学。
DOI：
10.1101/2021.02.04.429674
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Muller,FlorianL
中科院分区：
文献类型：
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作者：
Yan,VictoriaC;Pham,Cong-Dat;Yan,MatthewJ;Yan,AlexanderJ;Khadka,Sunada;Arthur,Kenisha;Ackroyd,JeffreyJ;Georgiou,DimitraK;Roon,LauraE;Bushman,LaneR;Anderson,PeterL;Li,Chun;Muller,FlorianL
尽管已被FDA批准用于COVID-19，但Remdesivir（Veklury®）的临床疗效仍存在争议。我们之前指出了其母体核苷GS-441524更适合COVID-19治疗的药代动力学、药效学和毒理学原因。在这里，我们评估了GS-441524在比格犬中的口服生物利用度，并表明血浆浓度比抗SARS-CoV-2的EC 50高约24倍，很容易且安全地维持。这些数据支持GS-441524作为COVID-19口服制剂的翻译。
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 EC50 against SARS-CoV-2 are easily and safely sustained. These data support translation of GS-441524 as an oral agent for COVID-19.