Finding the Dose for Hydroxychloroquine Prophylaxis for COVID-19: The Desperate Search for Effectiveness
Finding the Dose for Hydroxychloroquine Prophylaxis for COVID-19: The Desperate Search for Effectiveness
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DOI：
10.1002/cpt.1874
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发表时间：
2020-06-01
影响因子：
6.7
通讯作者：
Nicol, Melanie R.
中科院分区：
文献类型：
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作者：
Al-Kofahi, Mahmoud;Jacobson, Pamala;Nicol, Melanie R.
羟氯喹是一种抗疟疾药物，正在测试作为由严重急性呼吸系统综合征冠状病毒2引起的新型冠状病毒病2019（COVID-19）大流行的潜在治疗方法。尽管羟氯喹对COVID-19的疗效仍不确定，但它可能作为一种潜在的预防药物，特别是在高风险人群中，如医护人员、感染患者的家庭接触者和免疫功能低下者。我们的目标是通过模拟高感染风险人群，通过优化高于体外产生的半数最大有效浓度（EC 50）的暴露量，确定可能的羟氯喹给药方案，并帮助指导研究人员在COVID-19预防研究中选择剂量。在暴露前预防性治疗中，为了在> 50%的稳态受试者中维持每周谷值高于EC 50，需要800 mg负荷剂量，然后每周两次或三次给予400 mg。在暴露驱动的暴露后预防环境中，800 mg负荷剂量，然后在6小时内给予600 mg，然后每天600 mg，再持续4天，在> 50%的受试者中达到高于EC 50的每日谷值。这些剂量高于疟疾化学预防的推荐剂量，需要进行临床试验以确定安全性和有效性。
Hydroxychloroquine is an antimalarial drug being tested as a potential treatment for the novel coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2. Although the efficacy of hydroxychloroquine for COVID-19 remains uncertain, it may serve as a potential prophylactic agent especially in those at high risk, such as healthcare workers, household contacts of infected patients, and the immunocompromised. Our aim was to identify possible hydroxychloroquine dosing regimens through simulation in those at high risk of infections by optimizing exposures above the in vitro generated half maximal effective concentration (EC50) and to help guide researchers in dose-selection for COVID-19 prophylactic studies. To maintain weekly troughs above EC50 in > 50% of subjects at steady-state in a pre-exposure prophylaxis setting, an 800 mg loading dose followed by 400 mg twice or 3 times weekly is required. In an exposure driven, post-exposure prophylaxis setting, 800 mg loading dose followed in 6 hours by 600 mg, then 600 mg daily for 4 more days achieved daily troughs above EC50 in > 50% subjects. These doses are higher than recommended for malaria chemoprophylaxis, and clinical trials are needed to establish safety and efficacy.