How might this change clinical pharmacology or translational science?
Efficacy of nitazoxanide has been demonstrated for uncomplicated influenza and the presented predictions may help inform nitazoxanide dose selection for COVID-19 clinical trials.

Acknowledgements

The authors acknowledge Prof. David Back from the University of Liverpool for his advice and feedback on this manuscript. The authors also thank Articulate Science for publication support.

Author Contributions

All authors wrote the manuscript. A.O. and R.R. designed the research. U.A., H.B., L.T., H.P. and A.O. performed the research. R.R. and H.P. analysed the data.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Figure Legends Figure 1 Stimulated plasma (a ) and lung (b ) concentration for nitazoxanide 600 mg BID for 5 days with food relative to the average reported tizoxanide EC90 value for influenza strains (Table S1) similar to those in a previous phase 2b/3 trial in uncomplicated influenza [24].
Figure 2a Predicted tizoxanide Ctrough (BID – 12 h, TID – 8 h, QID – 6 h) for various dosing regimens of nitazoxanide in fasted state at the end of the first dose. Data are presented as mean and error bars represent standard deviation. The percentages adjacent to the bar chart indicate the percentages of simulated population over EC90 of nitazoxanide for SARS-CoV-2.
Figure 2b Predicted tizoxanide Ctrough (BID – 12 h, TID – 8 h, QID – 6 h) for various dosing regimens of nitazoxanide in fed state at the end of the first dose. Data are presented as mean and error bars represent standard deviation. The percentages adjacent to the bar chart indicate the percentages of simulated population over EC90 of nitazoxanide for SARS-CoV-2.
Figure 3 Predicted plasma and lung concentrations for optimal doses during the fed state at different regimens reaching steady state – (a ) 1400 mg BID, (b ) 900 mg TID and (c ) 700 mg QID. TIZ – tizoxanide, SD – standard deviation, solid red line indicates clinical Cmax of 1 g single dose at fed state [29], solid green line represents clinical Cmax of 500 mg single dose [54] at fed state and the dotted red line represents the EC90 of nitazoxanide for SARS-CoV-2 [44].