| DOI: 10.29090/psa.2021.03.20.197 | Pharm Sci Asia 2021; 48(3), 291-299 |
Optimized chloroquine phosphate dosage regimens for early virological clearance of severe acute respiratory syndrome coronavirus 2 using Monte Carlo simulationNattapong Tidwong1, Baralee Punyawudho1, Pannee Leelawattanachai2, Suwida Tangtrakultham3, Pitchaya Dilokpattanamongkol3, Taniya Paiboonvong4, Supatat Chumnumwat3, Preecha Montakantikul3*
1 Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand
2 Department of Pharmacy, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
3 Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand
4 Department of Pharmacy Practice, College of Pharmacy, Rangsit University, Pathum Thani, Thailand
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% PTAeff within 48-72 hours, while also maintained ≤1% PTAtox throughout the treatment course. Further clinical studies are needed to prove the efficacy and safety of our designed regimens.
Keyword:
Chloroquine; Monte Carlo; Pharmacokinetics; SARS-CoV-2; COVID-19
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