Dosing of hydroxychloroquine for SARS-CoV-2

March 26, 2020

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Chloroquine has been sporadically used to treat SARS-CoV-2 infection, and hydroxychloroquine shares the same mechanism of action as chloroquine while having a better safety profile. The authors were interested in whether the immunomodulatory effect of hydroxychloroquine can be used to control the cytokine storm that occurs in late-phase critically ill COVID-19 patients. The authors tested the pharmacological activity of chloroquine and hydroxychloroquine using SARS-CoV-2 infected Vero cells. They used these in vitro data to inform physiologically-based pharmacokinetic models (PBPK). Using these models, hydroxychloroquine concentrations in lung fluid were simulated under five different dosing regimens. They found that hydroxychloroquine (EC50 0.72 μM) was more potent than chloroquine (EC50 5.47 μM) in vitro. Based on the PBPK models, a loading dose of 400 mg BD of hydroxychloroquine sulfate was given orally, followed by a maintenance dose of 200 mg BD for 4 days. This dosing was three-times the potency of chloroquine phosphate when given 500 mg BD 5 days in advance. Therefore hydroxychloroquine is more potent than chloroquine in inhibiting SARS-CoV-2 in vitro.

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Yao X, Ye F, Zhang M, Cui C, Huang B, et al. ISSN: Clin Infect Dis; pii: ciaa237


Added: March 26, 2020