Need for highly concentrated dosing for the lungs
Studies by X. Yao et al and S. Perinel et al suggest that HCQ can prevent the acidification of intracellular organelles, inhibit lysosomal release of viral genome and interfere with the glycosylation of the angiotensin-converting enzyme-2 (ACE2) receptor on the host cell, reducing the binding efficiency between the receptor and spike protein on the surface of the coronavirus and thereby reducing the chances of COVID-19 infection and replication. Therefore, on the molecular and cellular levels, HCQ has been shown to achieve antiviral activity against SARS-CoV-2, the strain of coronavirus that causes COVID-19. A study by Fan et al, a pharmacokinetics review team from the US Food and Drug Administration (FDA), emphasized the importance of translating in vitro antiviral activity to appropriate clinical dosing regimens and concluded that “antiviral effect against SARS-Cov-2 [is] not likely achievable with a safe oral dosing regimen” of HCQ due to dose confinement by potential cardiotoxicity. The FDA revoked emergency use authorization for HCQ, and recent clinical trials studying orally administered HCQ, such as SOLIDARITY and RECOVERY, which proposed the highest dosing regimen of 1600mg on day 1 and 800mg the next 9 days, were halted. Fan et al suggested that “a strategy to increase the drug exposure at the site of action (e.g., through targeted delivery) while minimizing the systemic exposure may be desirable.”
