Population Pharmacokinetics of Remdesivir and GS-441524 in Hospitalized COVID-19 Patients
Emiel Leegwater, Dirk Jan A. R. Moes, Liesbeth Bosma, Thomas H. Ottens, I.M. van der Meer, Cees van Nieuwkoop, Erik B. Wilms
Abstract
) for GS-441524 in plasma can be improved by shortening the dose interval of remdesivir and thereby increasing the total daily dose (PTA, 51.4% versus 94.7%). In patients with reduced renal function, the metabolite GS-441524 accumulates. A population pharmacokinetic model for remdesivir and GS-441524 in COVID-19 patients was developed. Remdesivir showed highly variable pharmacokinetics. The elimination half-life of remdesivir in COVID-19 patients is short, and the clearance of GS-441524 is dependent on the eGFR. Alternative dosing regimens aimed at optimizing the remdesivir and GS-441524 concentrations may improve the effectiveness of remdesivir treatment in COVID-19 patients.