Abstract

1. During the recent COVID-19 outbreak hydroxychloroquine (HCQ) has been proposed as a safe and effective therapeutic option. However, a wide variety of dosing schemes has been applied in the clinical practice and tested in clinical studies.

2. An extended literature survey was performed investigating the pharmacokinetics, the efficacy and safety of HCQ in COVID-19 treatment. Population pharmacokinetic models were retrieved from the literature and after evaluation and assessment one was selected in order to perform simulations.

3. The most commonly applied dosing schemes were explored for patients with different weights and different levels of HCQ clearance impairment. Model-based simulations of HCQ concentrations revealed that high initial doses followed by low and sparse doses may offer significant benefits to patients by decreasing the viral load without reaching levels considered to produce adverse effects. For instance, the dosing scheme proposed for a 70 kg adult with moderate COVID-19 symptoms would be 600 mg upon diagnosis, 400 mg after 12 h, 300 mg after 24 h, 200 mg after 36 h, followed by 200 mg BID for 4 d, followed by 200 mg OD for 5 d.

4. Based on the results from simulations performed and the currently published knowledge regarding HCQ in COVID-19 treatment, this study provides evidence that a high loading dose followed by sparse doses could offer significant benefits to the patients.

 抽象的

1. 
   在最近的 COVID-19 爆发期间，羟氯喹 (HCQ) 被提议作为一种安全有效的治疗选择。然而，多种给药方案已应用于临床实践并在临床研究中进行了测试。

2. 
   进行了一项广泛的文献调查，调查了 HCQ 在 COVID-19 治疗中的药代动力学、有效性和安全性。从文献中检索群体药代动力学模型，并经过评估和评估后选择一个模型进行模拟。

3. 
   针对不同体重和不同 HCQ 清除障碍水平的患者探索了最常用的给药方案。基于模型的 HCQ 浓度模拟表明，高初始剂量随后低剂量和稀疏剂量可能会通过降低病毒载量而不会达到被认为产生不良影响的水平，从而为患者带来显着益处。例如，对于患有中度 COVID-19 症状的 70 公斤成人，建议的剂量方案为诊断时 600 毫克，12 小时后 400 毫克，24 小时后 300 毫克，36 小时后 200 毫克，然后 4 小时 BID 200 毫克。 d，随后 200 mg OD，持续 5 d。

4. 
   根据模拟结果以及目前公布的有关 HCQ 在 COVID-19 治疗中的知识，本研究提供的证据表明，高负荷剂量和稀疏剂量可以为患者带来显着益处。