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氯喹和羟氯喹治疗冠状病毒患者的药代动力学特性及毒性考量综述。

A review on the pharmacokinetic properties and toxicity considerations for chloroquine and hydroxychloroquine to potentially treat coronavirus patients.

作者信息

Askarian Fatemeh, Firoozi Zahra, Ebadollahi-Natanzi Alireza, Bahrami Solmaz, Rahimi Hamid-Reza

机构信息

Student Research Committee, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

Department of Medical Genetics, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

出版信息

Toxicol Res. 2021 Jul 19;38(2):137-148. doi: 10.1007/s43188-021-00101-5. eCollection 2022 Apr.

Abstract

The SARS-CoV-2 virus, caused a novel emerged coronavirus disease, is growing rapidly worldwide. Few studies have evaluated the efficacy and safety of Chloroquine (CQ), an old antimalarial drug, and Hydroxychloroquine (HCQ) in the treatment of COVID-19 infection. HCQ is derived from CQ by adding a hydroxyl group into it and is a less toxic derivative of CQ for the treatment of COVID-19 infection because it is more soluble. This article summarizes pharmacokinetic properties and toxicity considerations for CQ and HCQ, drug interactions, and their potential efficacy against COVID-19. The authors also look at the biochemistry changes and clinical uses of CQ and HCQ, and supportive treatments following toxicity occurs. It was believed that CQ and HCQ may provide few benefits to COVID-19 patients. A number of factors should be considered to keep the drug safe, such as dose, in vivo animal toxicological findings, and gathering of metabolites in plasma and/or tissues. The main conclusion of this review is that CQ and HCQ with considered to their ADMET properties has major shortcomings and fully irresponsible.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引发了一种新型冠状病毒疾病,正在全球迅速蔓延。很少有研究评估氯喹(CQ)这种古老的抗疟药物以及羟氯喹(HCQ)在治疗2019冠状病毒病(COVID-19)感染方面的疗效和安全性。HCQ是通过在CQ中添加一个羟基衍生而来的,并且由于其溶解性更强,是用于治疗COVID-19感染的毒性较小的CQ衍生物。本文总结了CQ和HCQ的药代动力学特性及毒性考量、药物相互作用以及它们对COVID-19的潜在疗效。作者还探讨了CQ和HCQ的生化变化及临床用途,以及毒性发生后的支持性治疗。曾有人认为CQ和HCQ可能对COVID-19患者益处不大。为确保用药安全,应考虑诸多因素,如剂量、体内动物毒理学研究结果以及血浆和/或组织中代谢物的聚集情况。本综述的主要结论是,考虑到CQ和HCQ的吸收、分布、代谢和排泄特性,它们存在重大缺陷且完全不可靠。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eba/8960546/4db63d209689/43188_2021_101_Fig1_HTML.jpg

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