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].