Optimizing hydroxychloroquine dosing regimen for treatment of pediatric patients with coronavirus disease 2019 using Monte Carlo simulation
Issued Date
2022-01-01
Resource Type
ISSN
25868195
eISSN
25868470
Scopus ID
2-s2.0-85123755080
Journal Title
Pharmaceutical Sciences Asia
Volume
49
Issue
1
Start Page
22
End Page
33
Rights Holder(s)
SCOPUS
Bibliographic Citation
Pharmaceutical Sciences Asia Vol.49 No.1 (2022) , 22-33
Suggested Citation
Treerattanapun L., Tangtrakultham S., Tidwong N., Montakantikul P. Optimizing hydroxychloroquine dosing regimen for treatment of pediatric patients with coronavirus disease 2019 using Monte Carlo simulation. Pharmaceutical Sciences Asia Vol.49 No.1 (2022) , 22-33. 33. doi:10.29090/PSA.2022.01.21.116 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/86684
Title
Optimizing hydroxychloroquine dosing regimen for treatment of pediatric patients with coronavirus disease 2019 using Monte Carlo simulation
Author's Affiliation
Other Contributor(s)
Abstract
Hydroxychloroquine may be used to treat COVID-19 infections when remdesivir is unavailable. There is currently no hydroxychloroquine dosage regimen for pediatrics with COVID-19 infections. We aimed to determine the optimal dosage regimen needed to rapidly achieve pharmacokinetic and pharmacodynamic (PKPD) targets for virological clearance in pediatrics. A 10,000-subject Monte Carlo simulation was performed to calculate probabilities of efficacy and safety attainment, using allometrically scaled PKPD targets based on published adult pharmacokinetic studies. Allometric scaling of hydroxychloroquine clearance was also performed. The simulation predicted the probability of target attainment (PTA) of each dosage regimen to achieve an 80% PTA and 80% cumulative fraction of response, with <10% PTA for toxicity. The loading dosage of 6 mg/kg/dose, four times daily for 2 days, was found to provide rapid virological clearance with a high PTA (92.2%) within 2 days of treatment. Maintenance dosage of 3.25 mg/kg/dose, three times daily for the next 8 days, achieved the appropriate plasma hydroxychloroquine level until treatment cessation, with a PTA >80%. As to safety, this dosage regimen achieved a PTA <10% of the safety target, giving a probability of cardiotoxicity of <0.01%. The optimal hydroxychloroquine regimen is the loading dosage of 6 mg/kg/dose, four times daily for 2 days, followed by maintenance dosage of 3.25 mg/kg/dose, three times daily, on days 3–10. This regimen achieves virological clearance of COVID-19 and low cardiotoxicity in pediatrics. However, clinical studies are needed to confirm its efficacy and safety.