Optimized Chloroquine Phosphate Dosage Regimens for Early Virological Clearance of Severe Acute Respiratory Syndrome Coronavirus 2 using Monte Carlo Simulation

• Main Authors: Nattapong Tidwong, Baralee Punyawudho, Pannee Leelawattanachai, Suwida Tangtrakultham, Pitchaya Dilokpattanamongkol, Taniya Paiboonvong, Supatat Chumnumwat, Preecha Montakantikul
• Other Authors: Rangsit University
• Format: Article
• Published: 2022
• Subjects: Medicine; Pharmacology, Toxicology and Pharmaceutics
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/78725
• Institution: Mahidol University

Chloroquine (CQ) exhibited promising in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the optimal dosage regimens remain unknown. Our objective was to explore the optimal chloroquine phosphate (CQP) dosage regimens for early achievement of virological clearance within 48-72 hours to diminish in-hospital transmission to front-line healthcare workers. A 10,000-subject Monte Carlo simulation was performed to calculate both probability of efficacy and safety attainment (PTA) using pharmacokinetic (PK) parameters obtained from the published population PK study. Dosage regimens that early achieved PTA of efficacy (PTAeff) ≥90% within 48-72 hours, while maintained PTA of toxicity (PTAtox) ≤1% were considered optimal. For the previously proposed regimens in published guidelines and clinical studies, all dosage regimens could not achieve ≥90% PTAeff, except one with the highest dosage regimen. Our simulations suggested that large amount of loading dose was required for the early achievement. We designed three dosage regimens containing high loading dose (2-3 gram per day), which early achieved ≥90% PTAeffwithin 48-72 hours, while also maintained ≤1% PTAtoxthroughout the treatment course. Further clinical studies are needed to prove the efficacy and safety of our designed regimens.