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Hydroxychloroquine as a Chemoprophylactic Agent for COVID-19: A Clinico-Pharmacological Review
Hydroxychloroquine has gained much attention as one of the candidate drugs that can be repurposed as a prophylactic agent against SARS-CoV-2, the agent responsible for the COVID-19 pandemic. Due to high transmissibility and presence of asymptomatic carriers and presymptomatic transmission, there is...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773916/ https://www.ncbi.nlm.nih.gov/pubmed/33390974 http://dx.doi.org/10.3389/fphar.2020.593099 |
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author | Agarwal, Mudit Ranjan, Piyush Baitha, Upendra Mittal, Ankit |
author_facet | Agarwal, Mudit Ranjan, Piyush Baitha, Upendra Mittal, Ankit |
author_sort | Agarwal, Mudit |
collection | PubMed |
description | Hydroxychloroquine has gained much attention as one of the candidate drugs that can be repurposed as a prophylactic agent against SARS-CoV-2, the agent responsible for the COVID-19 pandemic. Due to high transmissibility and presence of asymptomatic carriers and presymptomatic transmission, there is need for a chemoprophylactic agent to protect the high-risk population. In this review, we dissect the currently available evidence on hydroxychloroquine prophylaxis from a clinical and pharmacological point of view. In vitro studies on Vero cells show that hydroxychloroquine effectively inhibits SARS-CoV-2 by affecting viral entry and viral transport via endolysosomes. However, this efficacy has failed to replicate in in vivo animal models as well as in most clinical observational studies and clinical trials assessing pre-exposure prophylaxis and postexposure prophylaxis in healthcare workers. An analysis of the pharmacology of HCQ in COVID-19 reveals certain possible reasons for this failure—a pharmacokinetic failure due to failure to achieve adequate drug concentration at the target site and attenuation of its inhibitory effect due to the presence of TMPRSS2 in airway epithelial cells. Currently, many clinical trials on HCQ prophylaxis in HCW are ongoing; these factors should be taken into account. Using higher doses of HCQ for prophylaxis is likely to be associated with increased safety concerns; thus, it may be worthwhile to focus on other possible interventions. |
format | Online Article Text |
id | pubmed-7773916 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77739162021-01-01 Hydroxychloroquine as a Chemoprophylactic Agent for COVID-19: A Clinico-Pharmacological Review Agarwal, Mudit Ranjan, Piyush Baitha, Upendra Mittal, Ankit Front Pharmacol Pharmacology Hydroxychloroquine has gained much attention as one of the candidate drugs that can be repurposed as a prophylactic agent against SARS-CoV-2, the agent responsible for the COVID-19 pandemic. Due to high transmissibility and presence of asymptomatic carriers and presymptomatic transmission, there is need for a chemoprophylactic agent to protect the high-risk population. In this review, we dissect the currently available evidence on hydroxychloroquine prophylaxis from a clinical and pharmacological point of view. In vitro studies on Vero cells show that hydroxychloroquine effectively inhibits SARS-CoV-2 by affecting viral entry and viral transport via endolysosomes. However, this efficacy has failed to replicate in in vivo animal models as well as in most clinical observational studies and clinical trials assessing pre-exposure prophylaxis and postexposure prophylaxis in healthcare workers. An analysis of the pharmacology of HCQ in COVID-19 reveals certain possible reasons for this failure—a pharmacokinetic failure due to failure to achieve adequate drug concentration at the target site and attenuation of its inhibitory effect due to the presence of TMPRSS2 in airway epithelial cells. Currently, many clinical trials on HCQ prophylaxis in HCW are ongoing; these factors should be taken into account. Using higher doses of HCQ for prophylaxis is likely to be associated with increased safety concerns; thus, it may be worthwhile to focus on other possible interventions. Frontiers Media S.A. 2020-12-17 /pmc/articles/PMC7773916/ /pubmed/33390974 http://dx.doi.org/10.3389/fphar.2020.593099 Text en Copyright © 2020 Agarwal, Ranjan, Baitha and Mittal http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Agarwal, Mudit Ranjan, Piyush Baitha, Upendra Mittal, Ankit Hydroxychloroquine as a Chemoprophylactic Agent for COVID-19: A Clinico-Pharmacological Review |
title | Hydroxychloroquine as a Chemoprophylactic Agent for COVID-19: A Clinico-Pharmacological Review |
title_full | Hydroxychloroquine as a Chemoprophylactic Agent for COVID-19: A Clinico-Pharmacological Review |
title_fullStr | Hydroxychloroquine as a Chemoprophylactic Agent for COVID-19: A Clinico-Pharmacological Review |
title_full_unstemmed | Hydroxychloroquine as a Chemoprophylactic Agent for COVID-19: A Clinico-Pharmacological Review |
title_short | Hydroxychloroquine as a Chemoprophylactic Agent for COVID-19: A Clinico-Pharmacological Review |
title_sort | hydroxychloroquine as a chemoprophylactic agent for covid-19: a clinico-pharmacological review |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773916/ https://www.ncbi.nlm.nih.gov/pubmed/33390974 http://dx.doi.org/10.3389/fphar.2020.593099 |
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