Dose prediction for repurposing nitazoxanide in SARS-CoV-2 treatment or chemoprophylaxis.
Rajith K R RajoliHenry PertinezUsman ArshadHelen BoxLee TathamPaul CurleyMegan NearyJoanne SharpNeill J LiptrottAnthony ValentijnChristopher DavidSteven P RannardGhaith AljayyoussiShaun H PenningtonAndrew HillMarta BoffitoStephen A WardSaye H KhooPatrick G BrayPaul M O'NeillW Dave HongGiancarlo A BiaginiAndrew OwenPublished in: medRxiv : the preprint server for health sciences (2020)
The PBPK model predicted that it was possible to achieve plasma and lung tizoxanide concentrations, using proven safe doses of nitazoxanide, that exceed the EC 90 for SARS-CoV-2. The PBPK model describing tizoxanide plasma pharmacokinetics after oral administration of nitazoxanide was successfully validated against clinical data. This dose prediction assumes that the tizoxanide metabolite has activity against SARS-CoV-2 similar to that reported for nitazoxanide, as has been reported for other viruses. The model and the reported dosing strategies provide a rational basis for the design (optimising plasma and lung exposures) of future clinical trials of nitazoxanide in the treatment or prevention of SARS-CoV-2 infection.