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).
Level 5 - mechanism / opinion, no new human data
In vitro cell culture experiment and physiologically based pharmacokinetic (PBPK) simulation.
PubMed 32150618 · doi:10.1093/cid/ciaa237
What was done
Researchers assessed the in vitro antiviral activity of chloroquine and hydroxychloroquine against SARS-CoV-2 in infected Vero cell cultures. They integrated the in vitro parameters into physiologically based pharmacokinetic (PBPK) models to simulate hydroxychloroquine concentrations in lung fluid under five different dosing regimens.
What was found
Hydroxychloroquine inhibited SARS-CoV-2 in vitro with an EC50 of 0.72 μM, demonstrating greater potency than chloroquine (EC50 = 5.47 μM). PBPK modeling indicated that an oral loading dose of 400 mg twice daily followed by a maintenance dose of 200 mg twice daily for 4 days achieved three times the potency of 500 mg twice-daily chloroquine phosphate.
Why it matters
Early in the COVID-19 pandemic, this study established baseline in vitro comparative potency values and theoretical lung tissue concentration projections to guide initial clinical trial dosing for hydroxychloroquine.
Limits
The findings are restricted to non-human cell culture (Vero cells) and theoretical computational models. The study did not measure in vivo human pharmacokinetics, antiviral efficacy in living organisms, or clinical outcomes in COVID-19 patients.
Cited by
- context In vitro studies found hydroxychloroquine to be three times more potent at inhibiting SARS-CoV-2 than chloroquine phosphate.