[1]莫立乾,郑 萍.新型冠状病毒肺炎治疗药物:磷酸氯喹[J].南方医科大学学报,2020,(04):586-594.[doi:10.12122/j.issn.1673-4254.2020.04.22]
 Chloroquine phosphate: therapeutic drug for COVID-19[J].Journal of Southern Medical University,2020,(04):586-594.[doi:10.12122/j.issn.1673-4254.2020.04.22]
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新型冠状病毒肺炎治疗药物:磷酸氯喹()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2020年04期
页码:
586-594
栏目:
出版日期:
2020-04-30

文章信息/Info

Title:
Chloroquine phosphate: therapeutic drug for COVID-19
作者:
莫立乾郑 萍
关键词:
新型冠状病毒肺炎磷酸氯喹抗病毒药代动力学安全性
Keywords:
coronavirus disease 2019 chloroquine phosphate antiviral pharmacokinetics safety
DOI:
10.12122/j.issn.1673-4254.2020.04.22
文献标志码:
A
摘要:
2019年新型冠状病毒肺炎(COVID-19)爆发以来,多种抗病毒药物先后试用于临床一线,我国《新型冠状病毒肺炎诊疗方案(试行第六版)》首次将磷酸氯喹纳入抗冠状病毒治疗的试用药物。作为抗击疟疾与风湿病的经典老药,磷酸氯喹在临床已应用80余年,而其在各种抗病毒治疗中,也表现出良好的效果。在COVID-19治疗中,氯喹在体内外均表现出抗病毒作用,个别临床研究的初步结果表明,其效果可能优于洛匹那韦/利托那韦。氯喹主要通过在寄生虫食物泡内和细胞溶酶体中积聚,提高其pH值而发挥抗寄生虫和抗病毒作用。在COVID-19的治疗中氯喹可能影响血管紧张素转化酶-2(ACE2)的糖基化,而抑制SARS-CoV-2表面的S蛋白与ACE2受体结合进入宿主细胞。在氯喹长年的临床应用中,发现其药代动力学特征表现也较为特异,半衰期长(2.5 d~10 d),表观分布容积巨大,在肝、脾、肾、肺中的浓度高于血浆浓度达200~700倍,而其在全血、血浆和血清中浓度也存在较大的差异,不同种族和个体间亦是如此。因此,氯喹稳态血药浓度范围与疗效间的关系目前尚不明确。氯喹毒性主要与超剂量使用相关,而且治疗剂量与毒性剂量和致死剂量十分接近。一般认为,氯喹单次剂量(基质)超过20 mg/kg就会有毒性,而超过30 mg/kg就能致死。因此,本文就磷酸氯喹在COVID-19治疗中的一些研究现状,及其药代动力学特点,抗病毒治疗与机制,以及氯喹的安全性作一综述。
Abstract:
Since the outbreak of coronavirus disease 2019 (COVID-19) in the late 2019, a variety of antiviral drugs have been used in the first-line clinical trial. The Diagnostic and Treatment Protocol for COVID-19 (Trial Version 6) in China recommends chloroquine phosphate for the first time as an anti-coronavirus trial drug. As a classic drug for treatment of malaria and rheumatism, chloroquine phosphate has been used clinically for more than 80 years, and has also shown good results in the treatment of various viral infections. As the plasma drug concentration varies greatly among different races and individuals and due to its narrow treatment window, chloroquine in likely to accumulate in the body to cause toxicity. Among the treatment regimens recommended for COVID-19, reports concerning the safety of a short-term high-dose chloroquine regimen remain scarce. In this review, the authors summarize the current research findings of chloroquine phosphate in the treatment of COVID-19, and examine the pharmacokinetic characteristics, antiviral therapy, the therapeutic mechanism and safety of chloroquine.

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更新日期/Last Update: 2020-04-30