Chloroquine dosage regimen simulation for pediatric patients with coronavirus disease 2019

Abstract

Chloroquine (CQ) efficacy was shown in some coronavirus disease 2019 (COVID-19) adult clinical studies. However, its data in children is still limited. Therefore, this study aims to assess the suitability of the dosage regimens from the literature and regimens proposed by the authors for pediatric COVID-19 patients aged 2-12 years old. The efficacy pharmacodynamic (PD) target was calculated for CQ blood concentration based on the literature's successfully treated COVID-19 adult regimen. The safety PD targets were derived from the literature regarding any adverse effects (AEs) and QTc prolongation. The adult pharmacokinetic (PK) parameters were transformed into pediatrics by allometric scaling (AS) method. A 10,000-time Monte Carlo simulation (MCS) was performed to calculate the percentage of probability to target attainment (%PTA). The literature's regimens were not capable of achieving 90%PTA efficacy PD target. The proposed regimens without loading dose (LD) achieved the efficacy target at day 8-10 which was later than the proposed regimens with LD (day 4-7). The 90%PTA below any AEs target was achieved in the first few days of the literature and proposed regimens but was unavoidable thereafter. Nevertheless, the 90%PTA below QTc prolongation target was favorably achieved by all regimens. This study revealed that the proposed regimen with LD seems to be the optimal dosage regimen. Additional studies are needed to validate our proposed regimens, especially among early-stage COVID-19 patients and recent major variants.