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Pharmacokinetic Basis of the Hydroxychloroquine Response in COVID-19: Implications for Therapy and Prevention

Tarek et al., European Journal of Drug Metabolism and Pharmacokinetics, doi:10.1007/s13318-020-00640-6
Aug 2020  
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HCQ for COVID-19
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In Silico analysis of HCQ treatment showing concluding that HCQ may affect viral clearance if administered early enough when the virus is still confined to the pharyngeal cavity; HCQ's effects against SARS-CoV-2 might be exerted more through enhanced cell-mediated immunity than direct antiviral effects; and the effects of HCQ on SARS-CoV-2 viral load may be missed in clinical trials if measurements are not done at the peak of viral replication; and the effects are only evident at dosages able to guarantee a certain plasma drug concentration, i.e., > 400 mg/day.
Tarek et al., 11 Aug 2020, peer-reviewed, 2 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperHCQAll
Pharmacokinetic Basis of the Hydroxychloroquine Response in COVID-19: Implications for Therapy and Prevention
Mohammad Tarek, Andrea Savarino
European Journal of Drug Metabolism and Pharmacokinetics, doi:10.1007/s13318-020-00640-6
Background and Objectives Chloroquine/hydroxychloroquine has recently been the subject of intense debate regarding its potential antiviral activity against SARS-Cov-2, the etiologic agent of COVID-19. Some report possible curative effects; others do not. Therefore, the objective of this study was to simulate possible scenarios of response to hydroxychloroquine in COVID-19 patients using mathematical modeling. Methods To shed some light on this controversial topic, we simulated hydroxychloroquine-based interventions on virus/host cell dynamics using a basic system of previously published differential equations. Mathematical modeling was implemented using Python programming language v 3.7. Results According to mathematical modeling, hydroxychloroquine may have an impact on the amplitude of the viral load peak and viral clearance if the drug is administered early enough (i.e., when the virus is still confined within the pharyngeal cavity). The effects of chloroquine/hydroxychloroquine may be fully explained only when also considering the capacity of this drug to increase the death rate of SARS-CoV-2-infected cells, in this case by enhancing the cell-mediated immune response. Conclusions These considerations may not only be applied to chloroquine/hydroxychloroquine but may have more general implications for development of anti-COVID-19 combination therapies and prevention strategies through an increased death rate of the infected cells.
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