Pharmacokinetic Basis of the Hydroxychloroquine Response in COVID-19: Implications for Therapy and Prevention
Tarek et al.,
Pharmacokinetic Basis of the Hydroxychloroquine Response in COVID-19: Implications for Therapy and Prevention,
European Journal of Drug Metabolism and Pharmacokinetics, doi:10.1007/s13318-020-00640-6
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.
Abstract: European Journal of Drug Metabolism and Pharmacokinetics (2020) 45:715–723
https://doi.org/10.1007/s13318-020-00640-6
ORIGINAL RESEARCH ARTICLE
Pharmacokinetic Basis of the Hydroxychloroquine Response
in COVID‑19: Implications for Therapy and Prevention
Mohammad Tarek1 · Andrea Savarino2
Published online: 11 August 2020
© Springer Nature Switzerland AG 2020
Abstract
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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