新型抗甲型流感药物--Pimodivir

A novel anti-influenza A virus drug--Pimodivir

Pimodivir是Vertex Pharmaceuticals公司正在开发中的一种口服抗甲型流感药物,是一种非核苷类甲型流感病毒RNA依赖的RNA聚合酶(RdRp) PB2亚基抑制剂。临床前试验研究证实,Pimodivir可以有效抑制对金刚烷胺和神经氨酸酶抑制剂耐药的各类甲型流感病毒,并且与神经氨酸酶抑制剂类药物奥司他韦有协同作用。Ⅰ期临床试验结果证实在健康志愿者中,Pimodivir 600 mg每日2次的剂量没有安全性问题,并且Pimodivir和奥司他韦联合用药未出现与临床相关的药物-药物相互作用。Ⅱ期临床实验结果显示Pimodivir不仅可以降低患者的病毒载量,而且耐受性良好。本文就Pimodivir的基本信息、作用机制、药效学、药代动力学和临床研究等作一概述。

Pimodivir is an oral anti-influenza A drug being developed by Vertex Pharmaceuticals.It is a non-nucleoside inhibitor of RNA-dependent RNA polymerase(RdRp) PB2 subunit of influenza A virus.Pimodivir has potent inhibitory activity against various influenza A viruses,including amantadine and neuraminidase inhibitors resistant strains,and has synergistic effects with neuraminidase inhibitor oseltamivir.Phase I clinical trial results confirmed that combination use of Pimodivir and oseltamivir in healthy volunteers had no clinically significant drug-drug interactions,and no safety events were observed with Pimodivir 600 mg twice daily alone or in combination with oseltamivir 75 mg twice daily.Phase Ⅱ clinical trial showed that Pimodivir had potential to not only reduce viral load but also have a clinical impact on patients.Further trials are therefore warranted to assess Pimodivir comprehensively.This article reviews the basic information,mechanism of action,pharmacodynamics,pharmacokinetics and clinical studies of Pimodivir.