Rational dosing of HCQ for COVID-19_pre-print
Background: Hydroxychloroquine (HCQ) has in vitro activity against SARS-CoV-2. However, datato inform optimal human dosing are limited.Methods: We conducted Monte Carlo simulations of HCQ sulfate using a published populationpharmacokinetic model. The model informing our simulations described a 2-compartmentlinear model with first-order absorption with a lag, derived from plasma HCQ concentrationdata from 22 healthy adults and 69 patients with malaria. Using the final PK model, we performed 1000 simulations for the plasma concentrations of HCQ sulfate based on various approved dosages (i.e. acute malaria, autoimmune conditions) and proposed dosing regimensfor treatment of COVID-19. The results of simulations were used to derive the area under the concentration-time curve (AUC), maximal concentration, and time to maximal concentration for each evaluated regimen.Results: The use of a loading dose, as with acute malaria dosing, resulted in rapid achievementof maximal concentrations early in the treatment course, which were maintained with dailydosing thereafter. The use of once or twice daily doses without a loading dose led to slowlyincreasing plasma concentrations through day 10. Simulated regimens that employed an 800mg loading dose for adults (13 mg/kg for children) followed by 400 mg at 6 or 12 hours (6.5mg/kg for children) achieved the greatest AUC0-24.Conclusions: Based on our findings, along with established safety data from malarial studies,we believe that approved dosing for treatment acute malaria is the most reasonable and safestapproach if HCQ will be used to treat COVID-19.