Hayden F G, Jennings L, Robson R, Schiff G, Jackson H, Rana B, McClelland G, Ipe D, Roberts N, Ward P
University of Virginia School of Medicine, Department of Internal Medicine, Charlottesville, USA.
Antivir Ther. 2000 Sep;5(3):205-13.
Oseltamivir is the prodrug of Ro64-0802 (GS4071), a potent and selective inhibitor of influenza A and B virus neuraminidases. Three randomized, double-blind, placebo-controlled, parallel-group studies evaluated oral oseltamivir for early treatment (75 or 150 mg twice daily for 5 days) or prevention (75 mg once or twice daily for 7 days) of experimental influenza B virus infection in healthy susceptible adults. Treatment study A (n=60) demonstrated similar trends to treatment study B (n=117), in which 75 mg doses of oseltamivir introduced 24 h after inoculation reduced median area under curve (AUC) virus titre (oseltamivir, 22.7; placebo, 131.1 log10 TCID50 x h/ml; P=0.002) and duration of viral shedding (oseltamivir, 23.9 h; placebo, 95.8 h; P=0.0005). In prevention study C (n=58), oseltamivir did not reduce infection rates (85 versus 84%) but significantly reduced median AUC virus titre (10.0 versus 66.9 log10 TCID50 x h/ml; P=0.03) and duration of viral shedding (36 versus 84 h; P=0.03) compared with placebo. Oseltamivir was well tolerated. No emergence of drug-resistant variants was detected by testing last-day isolates (n=112) in neuraminidase inhibition assays. These results indicate that oseltamivir has significant antiviral activity in experimental human influenza B virus infection when used for prophylaxis or early treatment.
奥司他韦是Ro64-0802（GS4071）的前体药物，Ro64-0802是一种高效且具有选择性的甲型和乙型流感病毒神经氨酸酶抑制剂。三项随机、双盲、安慰剂对照、平行组研究评估了口服奥司他韦对健康易感成年人实验性乙型流感病毒感染的早期治疗（每日两次，每次75或150毫克，共5天）或预防作用（每日一次或两次，每次75毫克，共7天）。治疗研究A（n = 60）显示出与治疗研究B（n = 117）相似的趋势，在治疗研究B中，接种后24小时给予75毫克剂量的奥司他韦可降低曲线下面积（AUC）病毒滴度中位数（奥司他韦为22.7；安慰剂为131.1 log10 TCID50×h/ml；P = 0.002）以及病毒 shedding持续时间（奥司他韦为23.9小时；安慰剂为95.8小时；P = 0.0005）。在预防研究C（n = 58）中，奥司他韦未降低感染率（85%对84%），但与安慰剂相比，显著降低了AUC病毒滴度中位数（10.0对66.9 log10 TCID50×h/ml；P = 0.03）以及病毒 shedding持续时间（36对84小时；P = 0.03）。奥司他韦耐受性良好。在神经氨酸酶抑制试验中，通过检测最后一天的分离株（n = 112）未发现耐药变异株的出现。这些结果表明，奥司他韦在用于预防或早期治疗时，对实验性人类乙型流感病毒感染具有显著的抗病毒活性。
