Hornick R B, Togo Y, Mahler S, Iezzoni D
Bull World Health Organ. 1969;41(3):671-6.
Amantadine hydrochloride is the first drug to show promise as a practical anti-influenza agent. Several studies demonstrating a prophylactic effect in volunteers with induced A2 disease as well as in patients during A2 outbreaks have created the impetus for therapeutic trials. The widespread A2 influenza epidemic that occurred early in 1968 provided the opportunity for therapeutic evaluation in the USA.A total of 197 prison inmates with proven influenza agreed to participate in the 10-day double-blind evaluation of amantadine (100 mg, twice daily). Onset of therapy was approximately 20 hours after first subjective awareness of illness.Assessment of drug effectiveness was based on rapidity of resolution of illness. There was a significant increase in the number of drug-treated as against placebo patients in the "rapid resolver" group whereas individuals receiving placebo dominated the "slow resolver" group. Analysis of febrile responses indicated that amantadine-treated patients had significantly more rapid defervescence. Virus isolation studies revealed etiologically related virus in 90% of all volunteers during the first 5 days of therapy. It was apparent that clinical improvement was not correlated with disappearance of the virus. Nevertheless, the trials conducted during the influenza season of early 1968 indicated the therapeutic effect of amantadine hydrochloride. Administration of 100 mg, twice daily, for 10 days did not cause any adverse effects.
盐酸金刚烷胺是首个显示出有望成为实用抗流感药物的药物。多项研究表明,其对感染A2型流感病毒的志愿者以及A2型流感暴发期间的患者具有预防作用,这推动了治疗试验的开展。1968年初发生的A2型流感大流行,为在美国进行治疗评估提供了机会。共有197名确诊感染流感的监狱囚犯同意参与为期10天的盐酸金刚烷胺双盲评估试验(每日两次,每次100毫克)。治疗开始时间约为患者首次自觉患病后20小时。药物疗效评估基于疾病缓解的速度。在“快速康复者”组中,接受药物治疗的患者数量相较于接受安慰剂治疗的患者有显著增加,而在“康复缓慢者”组中,接受安慰剂治疗的患者占主导。对发热反应的分析表明,接受盐酸金刚烷胺治疗的患者退热明显更快。病毒分离研究显示,在治疗的前5天,90%的志愿者体内发现了与病因相关的病毒。显然,临床症状的改善与病毒消失并无关联。尽管如此,1968年初流感季节期间进行的试验表明了盐酸金刚烷胺的治疗效果。每日两次,每次100毫克,连续服用10天,未产生任何不良反应。