MAY 04, 2020
Scientists compared the pharmacological activity of chloroquine and hydroxychloroquine in cells infected with SARS-CoV-2.
The authors tested the activity of chloroquine and hydroxychloroquine in Vero cells infected with SARS-CoV-2, the virus that causes COVID-19. In vitro analysis of physiologically based pharmacokinetic models were separately calculated for each drug. With these models, hydroxychloroquine concentrations in lung fluid were simulated under 5 different dosing regimens.
Hydroxychloroquine demonstrated a superior in vitro antiviral effect compared with chloroquine due its pharmacokinetics (high accumulation in cells and a long elimination half-life). Based on the pharmacological models, a loading dose of 400 mg hydroxychloroquine twice daily followed by a maintenance dose of 200 mg twice daily for 4 days was 3 times more potent than chloroquine phosphate given 500 mg twice daily, 5 days in advance.
This was an in vitro study. Future clinical trials assessing the antiviral and potential immunomodulatory properties of hydroxychloroquine as well as the optimal dosing and safety profile are necessary before it can be used readily in clinical practice for SARS-CoV-2 infection.
Hydroxychloroquine was more potent than chloroquine at inhibiting SARS-CoV-2 in vitro. The in vitro antiviral activity data and predicted drug concentrations are useful to guide the design of dosing regimens in future clinical trials. Current clinical trials are investigating the use of hydroxychloroquine to treat COVID-19, but dosing regimens based mainly on past clinical experience may result in greater adverse effects. This in vitro study based on pharmacokinetic modeling with a high loading dose and low maintenance dose may be more optimal.