Figure 3.

Simulated human pharmacokinetics (PKs). The clinical dosing regimen of a 200 mg loading dose followed by 100 mg daily maintenance dose administered as 30‐minute I.V. infusion was simulated. Simulated PK profiles for (a) remdesivir (red) where the black dashed line indicate the remdesivir IC₅₀ (0.28 uM) and the black dotted line indicates remdesivir IC₉₀ (2.48 uM) for inhibiting SARS‐CoV‐2; (b) Nuc (blue) where the black dashed line indicates the Nuc IC₅₀ (0.62 uM) and the black dotted line indicates Nuc IC₉₀ (1.34 uM) for inhibiting SARS‐CoV‐2; and (c) TNuc (green) metabolites over a 5‐day period is shown. Free concentrations for parent and metabolites in uM are shown on a semi‐log scale. The mean observed peak concentration (C_max) measured in healthy volunteers is shown as black points. Error bars represent 95% confidence interval (CI) of observed data. The blue shaded region represents the 95% CI of the predicted Nuc plasma PK based on digitized human PK data described in the Supplementary Methods. IC₅₀, half‐maximal inhibitory concentration; IC₉₀, 90% inhibitory concentration; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2