Hayden F G, Osterhaus A D, Treanor J J, Fleming D M, Aoki F Y, Nicholson K G, Bohnen A M, Hirst H M, Keene O, Wightman K
University of Virginia, Charlottesville 22908, USA.
N Engl J Med. 1997 Sep 25;337(13):874-80. doi: 10.1056/NEJM199709253371302.
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.
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 < or =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.
Of 262 patients with confirmed influenza-virus 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< or =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.
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.
唾液酸类似物扎那米韦（GG167）是甲型和乙型流感病毒神经氨酸酶的选择性抑制剂。这些病毒酶对于病毒从感染细胞中释放至关重要，并且它们还可能减少呼吸道分泌物对病毒的灭活作用。当通过实验直接给予呼吸道时，扎那米韦具有强大的抗病毒作用。我们评估了扎那米韦在成人急性流感中的治疗活性。
在1994 - 1995年流感季节期间，我们在北美的38个中心和欧洲的32个中心分别进行了随机、双盲研究。共有417名持续时间≤48小时的流感样疾病成人被随机分配到三种治疗方法之一：经鼻喷雾给予6.4 mg扎那米韦加吸入10 mg，吸入10 mg扎那米韦加安慰剂喷雾，或两种途径均给予安慰剂。治疗由患者自行每日两次给药，持续五天。
在262例确诊为流感病毒感染的患者（占所有患者的63%）中，给予吸入和经鼻扎那米韦的88例患者以及仅给予吸入扎那米韦的85例患者，所有主要症状缓解的中位时间比给予安慰剂的89例患者短一天（分别为四天对五天，P = 0.02；四天对五天，P = 0.05）。在入组时发热的感染患者以及在症状发作后30小时内开始治疗的患者中，扎那米韦组主要症状缓解的中位时间均为四天，而安慰剂组为七天（P≤0.01）。给予吸入和经鼻扎那米韦组的鼻洗液病毒滴度显著低于安慰剂组。局部给予扎那米韦耐受性良好。
在患有甲型或乙型流感病毒感染的成人中，将选择性神经氨酸酶抑制剂扎那米韦直接给予呼吸道是安全的，并且如果早期开始使用可减轻症状。
