In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

by | CIRS, Functional & Integrative Medicine, ISEAI

https://www.ncbi.nlm.nih.gov/pubmed/32150618

Comment; Covid19 can rapidly progress to respiratory failure, cytokines are involved in regulating the immune response. An over-active immune system without the proper “brakes” can be as deadly as infection. Hydroxychloroquine helps keep those brakes ready to prevent loss of control.

Yao X1, Ye F2, Zhang M1, Cui C1, Huang B2, Niu P2, Liu X1, Zhao L2, Dong E3, Song C4, Zhan S5, Lu R2, Li H1,3, Tan W2, Liu D1.

Author information

Abstract

BACKGROUND:

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first broke out in Wuhan (China) and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late-phase in critically ill SARS-CoV-2 infected patients. Currently, there is no evidence to support the use of hydroxychloroquine in SARS-CoV-2 infection.

METHODS:

The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2 infected Vero cells. Physiologically-based pharmacokinetic models (PBPK) were implemented for both drugs separately by integrating their in vitro data. Using the PBPK models, hydroxychloroquine concentrations in lung fluid were simulated under 5 different dosing regimens to explore the most effective regimen whilst considering the drug’s safety profile.

RESULTS:

Hydroxychloroquine (EC50=0.72 μM) was found to be more potent than chloroquine (EC50=5.47 μM) in vitro. Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached three times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance.

CONCLUSIONS:

Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

Dr. Raymond Oenbrink
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