Combination of peramivir and rimantadine demonstrate synergistic antiviral effects in sub-lethal influenza A (H3N2) virus mouse model
Combination of peramivir and rimantadine demonstrate synergistic antiviral effects in sub-lethal influenza A (H3N2) virus mouse model
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DOI：
10.1016/j.antiviral.2010.09.020
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发表时间：
2010-12-01
影响因子：
7.6
通讯作者：
Babu, Y. S.
中科院分区：
文献类型：
--
作者：
Bantia, Shanta;Kellogg, Debra;Babu, Y. S.
在小鼠甲型流感/维多利亚/3/75 (H3N2) 模型中评估了肌肉注射神经氨酸酶 (NA) 抑制剂帕拉米韦和口服 M2 离子通道阻断剂金刚乙胺联合用药的疗效。用亚致死病毒剂量攻击小鼠（安慰剂组死亡率为0-40%），并通过三维效应分析来分析体重变化，以评估药物相互作用的模式。在病毒接种前1小时开始，在为期5天的治疗过程中给予化合物。帕拉米韦和金刚乙胺的剂量范围分别为0.3-3 mg/kg/d和5-30 mg/kg/d。在第10天，媒介物感染组观察到最大平均体重减轻5.19克。在1和3mg/kg/d帕拉米韦单药治疗组中，体重减轻分别为4.3和3.55克。分别。在金刚乙胺单药治疗组中，5、10 和 30 mg/kg/d 组的体重减轻分别为 3.43、2.1 和 1.64 g。 1 mg/kg/d 帕拉米韦与 5 和 10 mg/kg/d 金刚乙胺的组合分别产生了 1.69 和 0.69 的体重减轻（与媒介物和个体相比，p < 0.05），而 3.0 mg/kg/d 帕拉米韦与 10 和 30 mg/kg/d 金刚乙胺的组合没有显示任何体重减轻（与媒介物和个体相比，p < 0.05）代理）。所测试的大多数帕拉米韦和金刚乙胺药物组合的体重减轻的三维分析证明了协同抗病毒作用。 (C) 2010 Elsevier B.V. 保留所有权利。
Efficacy of combination of the intramuscularly administered neuraminidase (NA) inhibitor, peramivir, and the orally administered M2 ion channel blocker, rimantadine was evaluated in mouse influenza A/Victoria/3/75 (H3N2) model. Mice were challenged with a sub-lethal virus dose (0-40% mortality in placebo group) and changes in body weights were analyzed by three-dimensional effect analysis to assess mode of drug interactions.Compounds were administered in a 5-day treatment course starting 1 h before viral inoculation. The peramivir and rimantadine doses ranged from 0.3-3 mg/kg/d and 5-30 mg/kg/d, respectively. The maximum mean weight loss of 5.19 g was observed in the vehicle-infected group on day 10. In the 1 and 3 mg/kg/d peramivir monotherapy groups, the weight losses were 4.3 and 3.55 g. respectively. In the rimantadine monotherapy group, the weight losses were 3.43, 2.1, and 1.64 g for the 5, 10, and 30 mg/kg/d groups, respectively. Combination of 1 mg/kg/d peramivir with 5 and 10 mg/kg/d rimantadine produced weight losses of 1.69 and 0.69 (p < 0.05 vs. vehicle and individual agent), respectively, whereas the combination of 3.0 mg/kg/d peramivir with 10 and 30 mg/kg/d rimantadine did not show any weight loss (p < 0.05 vs. vehicle and individual agent). The three-dimensional analysis of the weight loss for the majority of the drug combinations of peramivir and rimantadine tested demonstrated synergistic antiviral effects. (C) 2010 Elsevier B.V. All rights reserved.