Department of Biological Sciences, BioCryst Pharmaceuticals, Inc., Birmingham, AL 35244, USA.
Antiviral Res. 2010 Dec;88(3):276-80. doi: 10.1016/j.antiviral.2010.09.020. Epub 2010 Oct 11.
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 1h 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 1mg/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.
在小鼠甲型流感 A/Victoria/3/75（H3N2）模型中评估了肌肉内给予神经氨酸酶（NA）抑制剂帕拉米韦和口服给予 M2 离子通道阻滞剂金刚烷胺的联合疗效。用亚致死剂量的病毒（安慰剂组死亡率为 0-40%）对小鼠进行攻毒，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，用 5 天的治疗方案给予化合物。帕拉米韦和金刚烷胺的剂量范围分别为 0.3-3mg/kg/d 和 5-30mg/kg/d。在第 10 天，在载体感染组中观察到最大平均体重减轻 5.19g。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 3.55g。在金刚烷胺单药治疗组中，5、10 和 30mg/kg/d 组的体重减轻分别为 3.43、2.1 和 1.64g。1mg/kg/d 帕拉米韦与 5 和 10mg/kg/d 金刚烷胺联合使用可导致体重减轻 1.69 和 0.69（p<0.05 与载体和单药相比），而 3.0mg/kg/d 帕拉米韦与 10 和 30mg/kg/d 金刚烷胺联合使用则未导致体重减轻（p<0.05 与载体和单药相比）。对测试的大多数帕拉米韦和金刚烷胺联合用药的体重减轻进行三维分析显示出协同的抗病毒作用。
