Vaccine Research Institute, Kitasato Daiichi Sankyo Vaccine Co. Ltd., 1-16-13, Kitakasai, Edogawa-ku, Tokyo, Japan.
Division of Virology, Institute of Medical Science, University of Tokyo, Japan.
J Infect Chemother. 2019 Aug;25(8):584-588. doi: 10.1016/j.jiac.2019.02.023. Epub 2019 Mar 29.
Four neuraminidase (NA) inhibitors and an RNA synthesis inhibitor were recently approved and are currently in clinical use for influenza. Among NA inhibitors, oseltamivir phosphate (OSE, Tamiflu) and zanamivir are approved worldwide, whereas peramivir and laninamivir octanoate (LAN, Inavir) are regionally approved for human use. Therefore, OSE has been used to treat infections of highly pathogenic influenza viruses, such as H5N1 and H7N9, which caused epidemic in southeast Asia and Egypt, and China, respectively. Generally, OSE is administered twice daily for 5 days by oral administration, and LAN once by inhalation for completing influenza therapy. In this study, we compared the efficacy of OSE and LAN administered according to the regimens in mice infected with highly lethal influenza viruses. The drugs were administered at the early and late stages of infection, which correspond to mild and severe inflammation in the lungs, respectively. Based on the drugs' regimens for human, a single administration of LAN at both stages of inflammation showed superior efficacy to repeated administration of OSE. LAN, as in OSE, could also be efficacious in treating severe influenza in humans.
四种神经氨酸酶（NA）抑制剂和一种 RNA 合成抑制剂最近获得批准并已在临床上用于流感治疗。在神经氨酸酶抑制剂中，磷酸奥司他韦（OSE，达菲）和扎那米韦在全球范围内获得批准，而帕拉米韦和拉尼米韦辛酯（LAN，依乐韦）仅在某些地区被批准用于人类。因此，OSE 已被用于治疗高致病性流感病毒（如 H5N1 和 H7N9）感染，这些病毒分别在东南亚和埃及以及中国引发了疫情。一般来说，OSE 通过口服给药，每日两次，连续 5 天，而 LAN 则通过吸入给药一次即可完成流感治疗。在这项研究中，我们比较了根据感染高致死性流感病毒的小鼠的方案给予 OSE 和 LAN 的疗效。药物在感染的早期和晚期给予，分别对应于肺部的轻度和重度炎症。根据药物对人类的方案，在炎症的两个阶段单次给予 LAN 比重复给予 OSE 更有效。LAN 与 OSE 一样，也可能对治疗人类严重流感有效。
