Nicol Melanie R, Joshi Abhay, Rizk Matthew L, Sabato Philip E, Savic Radojka M, Wesche David, Zheng Jenny H, Cook Jack
Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.
Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Clin Pharmacol Ther. 2020 Dec;108(6):1135-1149. doi: 10.1002/cpt.1993. Epub 2020 Sep 1.
Chloroquine and hydroxychloroquine are quinoline derivatives used to treat malaria. To date, these medications are not approved for the treatment of viral infections, and there are no well-controlled, prospective, randomized clinical studies or evidence to support their use in patients with coronavirus disease 2019 (COVID-19). Nevertheless, chloroquine and hydroxychloroquine are being studied alone or in combination with other agents to assess their effectiveness in the treatment or prophylaxis for COVID-19. The effective use of any medication involves an understanding of its pharmacokinetics, safety, and mechanism of action. This work provides basic clinical pharmacology information relevant for planning and initiating COVID-19 clinical studies with chloroquine or hydroxychloroquine, summarizes safety data from healthy volunteer studies, and summarizes safety data from phase II and phase II/III clinical studies in patients with uncomplicated malaria, including a phase II/III study in pediatric patients following administration of azithromycin and chloroquine in combination. In addition, this work presents data describing the proposed mechanisms of action against the severe acute respiratory distress syndrome coronavirus-2 and summarizes clinical efficacy to date.
氯喹和羟氯喹是用于治疗疟疾的喹啉衍生物。迄今为止,这些药物尚未被批准用于治疗病毒感染,也没有经过充分对照、前瞻性、随机的临床研究或证据支持其在2019冠状病毒病(COVID-19)患者中的使用。尽管如此,氯喹和羟氯喹正在单独或与其他药物联合进行研究,以评估它们在治疗或预防COVID-19方面的有效性。任何药物的有效使用都需要了解其药代动力学、安全性和作用机制。这项工作提供了与规划和启动使用氯喹或羟氯喹的COVID-19临床研究相关的基础临床药理学信息,总结了健康志愿者研究的安全性数据,并总结了非复杂性疟疾患者的II期和II/III期临床研究的安全性数据,包括一项儿科患者在联合使用阿奇霉素和氯喹后的II/III期研究。此外,这项工作还展示了描述针对严重急性呼吸综合征冠状病毒2的拟议作用机制的数据,并总结了迄今为止的临床疗效。