Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza virus infections
Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza virus infections
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DOI：
10.1056/nejm199709253371302
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发表时间：
1997-09-25
影响因子：
158.5
通讯作者：
Wightman, K
中科院分区：
文献类型：
--
作者：
Hayden, FG;Osterhaus, ADME;Wightman, K
背景唾液酸类似物扎那米韦（GG 167）是甲型和B型流感病毒神经氨酸酶的选择性抑制剂。这些病毒酶对于从受感染细胞释放病毒是必需的，并且它们还可以减少呼吸道分泌物对病毒的灭活。当实验性地直接给药于呼吸道时，扎那米韦具有有效的抗病毒作用。我们评估了扎那米韦在成人急性influense.Methods的治疗活性，我们进行了单独的随机，双盲研究，在38个中心在北美和32个中心在欧洲流感季节的1994-1995年。共有417名患有流感样疾病的成年人，持续时间小于或等于48小时，被随机分配到三种治疗中的一种：6.4 mg扎那米韦鼻内喷雾加10 mg吸入，10 mg扎那米韦吸入加安慰剂喷雾，或两种途径的安慰剂。治疗采用自我管理，每日2次，连续5天。（63%的患者），所有主要症状缓解的中位时间短一天在88名接受吸入和鼻内扎那米韦治疗的患者中，（P=0.02）和85例患者吸入扎那米韦单独（P=0.05）比89例患者给予安慰剂。在入组时发热的感染患者和症状发作后30小时内开始治疗的患者中，两个扎那米韦组的主要症状缓解的中位时间为4天，安慰剂组为7天（P小于或等于0.01）。吸入和鼻内给予扎那米韦的组的鼻洗液的病毒滴度显著低于安慰剂组。局部给药的扎那米韦是良好的tolerated.Conclusions在成人流感A或B病毒感染，直接管理的选择性神经氨酸酶抑制剂，扎那米韦，呼吸道是安全的，并减少症状，如果早期开始。(C)1997年，马萨诸塞州医学会。
Background The sialic acid analogue zanamivir (GG167) is a selective inhibitor of influenza A and B virus neuraminidases. These viral enzymes are essential for the release of virus from infected cells, and they may also reduce the inactivation of virus by respiratory secretions. When administered experimentally directly to the respiratory tract, zanamivir has potent antiviral effects. We assessed the therapeutic activity of zanamivir in adults with acute influenza.Methods We conducted separate randomized, double-blind studies in 38 centers in North America and 32 centers in Europe during the influenza season of 1994-1995. A total of 417 adults with influenza-like illness of less than or equal to 48 hours' duration were randomly assigned to one of three treatments: 6.4 mg of zanamivir by intranasal spray plus 10 mg by inhalation, 10 mg of zanamivir by inhalation plus placebo spray, or placebo by both routes. Treatments were self-administered twice daily for five days.Results Of 262 patients with confirmed influenzavirus infection (63 percent of all patients), the median length of time to the alleviation of all major symptoms was one day shorter (four days vs. five days) in the 88 patients given inhaled and intranasal zanamivir (P=0.02) and the 85 patients given inhaled zanamivir alone (P=0.05) than in the 89 patients given placebo. Among the infected patients who were febrile at enrollment and among those who began treatment within 30 hours after the onset of symptoms, the median time to the alleviation of major symptoms was four days in both zanamivir groups and seven days in the placebo group (P less than or equal to 0.01). Viral titers of nasal washings in the group given inhaled and intranasal zanamivir were significantly lower than those in the placebo group. The topically administered zanamivir was well tolerated.Conclusions In adults with influenza A or B virus infections, direct administration of a selective neuraminidase inhibitor, zanamivir, to the respiratory tract is safe and reduces symptoms if begun early. (C) 1997, Massachusetts Medical Society.