Barroso Luis, Treanor John, Gubareva Larisa, Hayden Frederick G
Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA.
Antivir Ther. 2005;10(8):901-10.
Oseltamivir is the only oral neuraminidase inhibitor currently available; we determined the tolerability and antiviral efficacy of oral peramivir for treatment and prophylaxis of experimental human influenza A and B.
288 susceptible, healthy volunteers (ages 18-45) were inoculated intranasally with A/Texas/36/ 91/H1N1 or B/Yamagata/16/88 virus in four randomized, double-blind, placebo-controlled trials.
For treatment dosing was initiated at 24 h after inoculation with peramivir doses ranging from 100-800 mg/day for 5 days. For prophylaxis dosing was initiated 24 h before inoculation and continued for 4 days with peramivir doses ranging from 50-800 mg/day.
The primary outcome measure for treatment was quantitative viral detection defined by the area under the curve (AUC) for nasal wash viral titres. For prophylaxis the primary outcome measure was the incidence of virus recovery.
In influenza A treatment, peramivir 400 mg q24h and 200mg q12h, but not lower doses, resulted in significant reductions in viral titre AUC. In influenza B treatment, both 400 and 800/400 mg once daily dose groups reduced AUC values. In influenza A prophylaxis, the percentage of individuals with nasal viral shedding did not differ significantly in the placebo (58%), 50 mg (61%), 200 mg (37%) and 400 mg (31%) dose groups. In influenza B prophylaxis, shedding frequencies were similar in placebo (55%), 200 mg (41%), 400 mg (35%) and 800 mg (47%) dose groups. The drug was well tolerated in all four studies, with nausea and headache being the most common side effects. No drug-resistant variants were detected.
Early treatment with peramivir was associated with significant antiviral effects in experimentally induced influenza in humans. Prophylaxis did not significantly reduce viral shedding. The relatively low blood peramivir concentrations observed may explain the lack of more robust antiviral effects, and parenteral dosing should be studied.
奥司他韦是目前唯一可用的口服神经氨酸酶抑制剂；我们确定了口服帕拉米韦治疗和预防实验性甲型和乙型人流感的耐受性和抗病毒疗效。
在四项随机、双盲、安慰剂对照试验中，288名易感健康志愿者（年龄18 - 45岁）经鼻接种A/德克萨斯/36/91/H1N1或B/山形/16/88病毒。
治疗时，接种后24小时开始给药，帕拉米韦剂量为100 - 800毫克/天，持续5天。预防时，接种前24小时开始给药，持续4天，帕拉米韦剂量为50 - 800毫克/天。
治疗的主要结局指标是通过鼻洗液病毒滴度曲线下面积（AUC）定义的定量病毒检测。预防的主要结局指标是病毒检出率。
在甲型流感治疗中，帕拉米韦400毫克每24小时一次和200毫克每12小时一次，但更低剂量则不然，导致病毒滴度AUC显著降低。在乙型流感治疗中，每日一次剂量400毫克和800/400毫克组均降低了AUC值。在甲型流感预防中，安慰剂组（58%）、50毫克组（61%）、200毫克组（37%）和400毫克组（31%）中鼻腔病毒脱落个体的百分比无显著差异。在乙型流感预防中，安慰剂组（55%）、200毫克组（41%）、400毫克组（35%）和800毫克组（47%）中脱落频率相似。在所有四项研究中该药物耐受性良好，恶心和头痛是最常见的副作用。未检测到耐药变异株。
帕拉米韦早期治疗与人类实验性诱导流感的显著抗病毒作用相关。预防并未显著减少病毒脱落。观察到的相对较低的帕拉米韦血药浓度可能解释了缺乏更强抗病毒作用的原因，应研究胃肠外给药。
