Optimized dosing regimen of hydroxychloroquine for treatment of coronavirus disease 2019 using Monte Carlo simulation

Abstract

Optimized dosage regimens of hydroxychloroquine (HCQ) in coronavirus disease 2019 (COVID-19) are currently unknown. We aimed to determine regimens that rapidly achieved the pharmacokinetic-pharmacodynamic (PKPD) target for virological clearance in COVID-19 patients. Plasma HCQ concentration was simulated using a non-steady state, 2-compartment linear model. The plasma trough concentration (Ctrough) > 0.7 mg/L was used as the PKPD target. The loading dose of 800 mg three times daily and 1,200 mg twice daily achieved the target on the first day with the probability of target attainment (PTA) 97.53% and 82.63%, respectively. Maintenance dose of 200 mg three times daily and 400 mg twice daily provided PTA > 80% from day 3 through day 10 after the initiation of HCQ therapy. All proposed regimens had the PTA < 1% to achieve toxic level of 4 mg/L. The optimal dose regimens for early viral clearance in COVID-19 patients were HCQ 800 mg three times daily on the first day followed by 200 mg three times daily for 9 days, and HCQ 1,200 mg twice daily on the first day followed by 400 mg twice daily for 9 days. Further clinical study is needed to ensure clinical efficacy and safety of these regimens.