Clinical Evaluation of Amantadine-HCL in the Prophylaxis of Induced Influenza

Abstract

Amantadine hydrochloride is a synthetic salt of a symmetrical primary amine, shown by Davies and others [1], to have antiviral activity especially against A2 influenza virus (Fig. 1). Studies by these workers, conducted in tissue cultures, mice and chick embryos demonstrated that amantadine blocked or slowed viral penetration into host cells. Mice exposed to influenza virus and treated with this drug had enhanced survival rates and less tissue damage than untreated animals. Additional confirmatory investigations plus lack of significant toxicity prompted the assessment of amantadine in man. Preliminary evaluations of its prophylactic effectiveness in volunteers against induced A2 influenza infection were inconclusive. Failure to employ individuals free of demonstrable neutralizing antibodies against the challenge strain was responsible. Morris and others [2], have emphasized the necessity of selecting volunteers with no homotypic antibodies in order to be able to regularly produce influenza disease. This required a virus not previously epidemic in the area from which volunteers were to be drawn. Screening potential challenge strains of influenza virus indicated that Rockville/1/65 strain of A₂ influenza was best suited because about 10% of our volunteers lacked or had low levels of neutralizing antibodies against it.