Effects of the Combination of Favipiravir (T-705) and Oseltamivir on Influenza A Virus Infections in Mice
Effects of the Combination of Favipiravir (T-705) and Oseltamivir on Influenza A Virus Infections in Mice
复制标题
DOI：
10.1128/aac.00933-09
复制
发表时间：
2010-01-01
影响因子：
4.9
通讯作者：
Furuta, Yousuke
中科院分区：
文献类型：
--
作者：
Smee, Donald F.;Hurst, Brett L.;Furuta, Yousuke
联合法匹拉韦（T-705 [6-氟-3-羟基-2-吡嗪甲酰胺]）和奥司他韦治疗流感病毒A/NWS/33（H1 N1）、A/维多利亚/3/75（H3 N2）和A/鸭/MN/1525/81（H5 N1）感染。T-705在1.4至4.3 μ M时单独抑制细胞培养物中的病毒。奥司他韦在3.7、0.02和0.16 μ M的浓度下抑制细胞中的这三种病毒，在神经氨酸酶试验中分别在0.94、0.46和2.31 nM的浓度下抑制这三种病毒。通常在感染后24小时开始，每天两次对小鼠进行口服治疗，持续5至7天。5天奥司他韦治疗（0.1和0.3 mg/kg/天）与20 mg/kg体重/天的T-705联合治疗H1N1感染的存活率明显更好。H3 N2感染的治疗需要50 mg/kg/天的奥司他韦7天，以达到60%的保护; 25 mg/kg/天无效。T-705在50至100 mg/kg/天剂量下具有>= 70%的保护性，但在25 mg/kg/天剂量下无活性。联合使用抑制剂（各25 mg/kg/天）可将存活率提高至90%。H5 N1感染并没有通过奥司他韦治疗而获益（
Favipiravir (T-705 [6-fluoro-3-hydroxy-2-pyrazinecarboxamide]) and oseltamivir were combined to treat influenza virus A/NWS/33 (H1N1), A/Victoria/3/75 (H3N2), and A/Duck/MN/1525/81 (H5N1) infections. T-705 alone inhibited viruses in cell culture at 1.4 to 4.3 mu M. Oseltamivir inhibited these three viruses in cells at 3.7, 0.02, and 0.16 mu M and in neuraminidase assays at 0.94, 0.46, and 2.31 nM, respectively. Oral treatments were given twice daily to mice for 5 to 7 days starting, generally, 24 h after infection. Survival resulting from 5 days of oseltamivir treatment (0.1 and 0.3 mg/kg/day) was significantly better in combination with 20 mg/kg of body weight/day of T-705 against the H1N1 infection. Treatment of the H3N2 infection required 50 mg/kg/day of oseltamivir for 7 days to achieve 60% protection; 25 mg/kg/day was ineffective. T-705 was >= 70% protective at 50 to 100 mg/kg/day but inactive at 25 mg/kg/day. The combination of inhibitors (25 mg/kg/day each) increased survival to 90%. The H5N1 infection was not benefited by treatment with oseltamivir (