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

Coronavirus disease 2019 (COVID-19) is an outbreak of acute respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Fourteen percent of patients developed severe illness requiring oxygen therapy and approximately 5% have multi-organ dysfunction requiring intensive care unit (ICU) treatment 1 .Multiple host factors were associated with severity including age ≥ 50 years, male sex, cardiovascular disease, diabetes, and malignancy 2 .However, there have not been any medications or other therapeutic options presently approved by the U.S. Food and Drug Administration (FDA) 3 .Hydroxychloroquine (HCQ) is currently being distributed to selected hospitals by the government in several countries, based on in vitro data and clinical studies showing potential benefits 4-6 .HCQ effectively inhibits viral replication by elevating the pH of endosomes and lysosomes 7 .Their anti-inflammatory properties that were demonstrated in the treatment of autoimmune diseases, may also reduce the inflammatory response to viral infection 8 .Currently, there is no conclusive evidence to support the optimal dosing and duration of HCQ for the treatment of COVID-19.Several HCQ regimens have been proposed in in vitro studies including 400 mg twice daily followed by 200 mg daily for 4 days 7 .In Thailand, the current national guideline recommended the regimen of 600 mg twice daily on the first day followed by 400 mg daily for 4-9 days 6 .However, these regimens have not been