Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza - Randomized controlled trials for prevention and treatment
Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza - Randomized controlled trials for prevention and treatment
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DOI：
10.1001/jama.282.13.1240
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发表时间：
1999-10-06
影响因子：
120.7
通讯作者：
Straus, SE
中科院分区：
文献类型：
--
作者：
Hayden, FG;Treanor, JJ;Straus, SE
背景流感病毒神经氨酸酶被认为是病毒在人体内复制所必需的;然而，迄今为止，可用的神经氨酸酶抑制剂仅限于扎那米韦，其是局部给药的。目的确定扎那米韦的安全性、耐受性，口服神经氨酸酶抑制剂奥司他韦的抗病毒活性（GS 4104/Ro 64 -0796）用于预防和早期治疗实验感染的人中的流感。1997年6月至7月间进行的安慰剂对照试验。地点：美国两所大型大学医学院的个别酒店房间。参与者：117名健康成年志愿者（年龄18-40岁;中位年龄21岁）的受试者（血凝抑制抗体滴度小于或等于1：8）。干预所有受试者鼻内接种流感A/Texas/36/91（H1N1）病毒。对于预防性研究，口服奥司他韦（100 mg每日一次[n = 12]、100 mg每日两次[n = 12]或匹配安慰剂[n = 13]，在病毒接种前26小时开始）。对于治疗研究，给予相同的药物（20 mg、100 mg或200 mg每日两次，200 mg每日一次，或匹配的安慰剂[n = 16]，每组从接种后28小时开始）。结果在预防性研究中，12例安慰剂组和21例奥司他韦组中分别有8例（67%）和8例（38%）感染，其中安慰剂组和奥司他韦组的感染率分别为100%和100%，奥司他韦组和奥司他韦组的感染率分别为100%和100%。（P = 0.16;疗效61%）; 6例（50%）安慰剂组与0例奥司他韦组相比，
Context Influenza virus neuraminidase is thought to be essential for virus replication in humans; however, to date, available neuraminidase inhibitors are limited to zanamivir, which is topically administered.Objective To determine the safety, tolerability, and antiviral activity of oral neuraminidase inhibitor oseltamivir (GS4104/Ro64-0796) for prevention and the early treatment of influenza in experimentally infected humans.Design Two randomized, double-blind, placebo-controlled trials conducted between June and July 1997.Setting Individual hotel rooms; 2 large US university medical schools.Participants A total of 117 healthy adult volunteers (aged 18-40 years; median age, 21 years) who were susceptible (hemagglutination-inhibition antibody titer less than or equal to 1:8).Interventions All subjects were inoculated intranasally with influenza A/Texas/36/91 (H1N1) virus. For the prophylaxis study, oral oseltamivir (100 mg once daily [n = 12], 100 mg twice daily [n = 12], or matching placebo [n = 13], starting 26 hours before virus inoculation) was administered. For the treatment study, the same drug was given (20 mg, 100 mg, or 200 mg twice daily, 200 mg once daily, or matching placebo [n = 16], in each group starting 28 hours after inoculation). All regimens were continued for 5 days.Main Outcome Measures Comparing placebo groups with pooled treatment groups, for prophylaxis, outcomes included frequency of infection and viral shedding; for treatment, viral shedding in titers.Results In the prophylaxis study, 8 (67%) of 12 placebo and 8 (38%) of 21 oseltamivir recipients became infected (P = .16; efficacy, 61%); 6 (50%) placebo compared with 0 oseltamivir recipients shed virus (P