Department of Pathology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
Antimicrob Agents Chemother. 2011 Nov;55(11):4961-70. doi: 10.1128/AAC.00412-11. Epub 2011 Aug 15.
We evaluated the efficacy of a single intravenous dose peramivir for treatment of influenza B virus infection in ferrets and cynomolgus macaques in the present study. A single dose of peramivir (60 mg/kg of body weight) given to ferrets on 1 day postinfection with influenza B virus significantly reduced median area under the curve (AUC) virus titers (peramivir, 8.3 log(10) 50% tissue culture infective doses [TCID(50)s] · day/ml; control, 10.7 log(10) TCID(50)s · day/ml; P < 0.0001). Furthermore, nasal virus titers on day 2 postinfection in ferrets receiving a single injection of peramivir (30 mg/kg) and AUCs of the body temperature increase in ferrets receiving a single injection of peramivir (30 and 60 mg/kg) were lower than those in ferrets administered oral oseltamivir phosphate (30 and 60 mg/kg/day twice daily for 3 days). In macaques infected with influenza B virus, viral titers in the nasal swab fluid on days 2 and 3 postinfection and body temperature after a single injection of peramivir (30 mg/kg) were lower than those after oral administration of oseltamivir phosphate (30 mg/kg/day for 5 days). The two animal models used in the present study demonstrated that inhibition of viral replication at the early time point after infection was critical in reduction of AUCs of virus titers and interleukin-6 production, resulting in amelioration of symptoms. Our results shown in animal models suggest that the early treatment with a single intravenous injection of peramivir is clinically recommended to reduce symptoms effectively in influenza B virus infection.
在本研究中，我们评估了单次静脉注射帕拉米韦治疗乙型流感病毒感染雪貂和食蟹猴的疗效。感染乙型流感病毒后第 1 天给雪貂单剂量 60mg/kg 的帕拉米韦，可显著降低中位病毒曲线下面积（AUC）病毒滴度（帕拉米韦，8.3log1050%组织培养感染剂量[TCID50]·天/ml；对照，10.7log10TCID50·天/ml；P<0.0001）。此外，感染后第 2 天雪貂接受单次注射帕拉米韦（30mg/kg）的鼻病毒滴度和接受单次注射帕拉米韦（30 和 60mg/kg）的体温 AUC 均低于接受口服磷酸奥司他韦的雪貂（30 和 60mg/kg/天，每日 2 次，连用 3 天）。在感染乙型流感病毒的食蟹猴中，感染后第 2 和第 3 天鼻拭子病毒滴度和单次注射帕拉米韦（30mg/kg）后的体温均低于口服奥司他韦磷酸酯（30mg/kg/天，连用 5 天）。本研究中使用的两种动物模型表明，感染后早期抑制病毒复制对于降低 AUC 病毒滴度和白细胞介素-6 产生至关重要，从而改善症状。我们在动物模型中获得的结果表明，早期单次静脉注射帕拉米韦治疗可有效减轻乙型流感病毒感染的症状，临床上值得推荐。
