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Amantadine Hydrochloride: Title and subTitle BreakAnalysis of Data Related to Its Proposed Use for Prevention of A2 Influenza Virus Disease in Human Beings FREE

Albert B. Sabin, MD
[+] Author Affiliations

Reprint requests to the Children's Hospital Research Foundation, Elland Ave and Bethesda, Cincinnati 45229.


JAMA. 1967;200(11):943-950. doi:10.1001/jama.1967.03120240071011
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The control of viral respiratory disease by safe and effective drugs is an important research goal, but the usefulness of potential candidates must be evaluated with great care. E. I. Du Pont de Nemours & Company, Wilmington, Del, has recently proposed that amantadine hydrochloride (1-adamantanamine hydrochloride) be used for the prophylaxis of A2 influenza virus disease in human beings. This proposal, based to a large extent on unpublished studies on human beings, led to the present analysis of both the published data and the unpublished reports; the investigators who carried out the studies have given permission to refer to the unpublished data in this communication.

Studies in Tissue Cultures, Eggs, and Experimental Animals 

Tissue Culture Studies.—  Investigators1-3 at the Du Pont laboratories reported that amantadine hydrochloride has an inhibitory effect on the influenza A, Al, and A2 strains that were tested and also on influenza C, the Sendai strain

REFERENCES

Davies, W.L., et al:  Antiviral Activity of 1-Adamantanamine . Science 144:862-863 ( (May 15) ) 1964;.
Neumayer, E.M.; Haff, R.F.; and Hoffman, C.E.:  Antiviral Activity of Amantadine Hydrochloride in Tissue Culture and in ovo , Proc Soc Exp Biol Med 119:393-396 ( (June) ) 1965;.
Hoffman, C.E., et al:  Mode of Action of the Antiviral Activity of Amantadine in Tissue Culture , J Bact 90:623-628 ( (Sept) ) 1965;.
Schild, G.C., and Sutton, E.N.P.:  Inhibition of Influenza Viruses in vitro and in vivo by 1-Adamantanamine Hydrochloride . Brit J Exp Path 46:263-273 ( (June) ) 1965;.
Cochran, K.W., et al:  Studies on the Antiviral Activity of Amantadine Hydrochloride , Ann NY Acad Sci 130:432-439 ( (July 30) ) 1965;.
Tyrrell, D.A.J.; Bynoe, M.L.; and Hoorn, B.:  Studies on the Antiviral Activity of 1-Adamantanamine , Brit J Exp Path 46:370-375 ( (Aug) ) 1965;.
Maassab, H.F., and Cochran, K.W.:  Rubella Virus: Inhibition in Vitro by Amantadine Hydrochloride , Science 145:1443-1444 ( (Sept 25) ) 1964;.
Cusumano, C.L., et al:  Effect of Amantadine Hydrochloride on Rubella Virus in Tissue Culture and in Ferrets , abstracted, Bact Proc , 1965;, p 119.
Plotkin, S.A.:  Inhibition of Rubella Virus by Amantadine , Arch Ges Virusforsch 16:438-442, 1965;.
Grunert, R.R.; McGahen, J.W.; and Davies, W.L.:  The in vivo Antiviral Activity of 1-Adamantanamine (Amantadine): I. Prophylactic and Therapeutic Activity Against Influenza Virus , Virology 26:262-269 ( (June) ) 1965;.
Jackson, G.G.; Muldoon, R.L.; and Akers, L.W.:  Serological Evidence for Prevention of Influenzal Infection in Volunteers by an Anti-Influenzal Drug Adamantanamine Hydrochloride , Antimicrob Agents Chemother 3:703-707, 1963;.
Hornick, R.B.; Togo, Y.; and Dawkins, A.T.:  Prophylactic Efficacy of Amantadine HCl in Volunteers With Experimentally Induced A2 Influenza Infection , abstracted; Bact Proc , 1966;, p 131.
Stanley, E.D., et al:  Evaluation of Antiviral Drugs: The Effect of Amantadine on Influenza in Volunteers , Ann NY Acad Sci 130:44-51 ( (July 30) ) 1965;.
Wendel, H.A.; Snyder, M.T.; and Pell, S.:  Trial of Amantadine in Epidemic Influenza , Clin Pharmacol Ther 7:38-43 ( (Jan) -Feb) 1966;.
Quilligan, J.J., Jr.; Hirayama, M.; and Baernstein, H.D., Jr.:  The Supression of A2 Influenza in Children by the Chemoprophylactic Use of Amantadine , J Pediat 69:572-575 ( (Oct) ) 1966;.
Finklea, J.T.; Hennessy, A.V.; and Davenport, F.M.:  A Field Trial of Amantadine Prophylaxis in Naturally Occurring Acute Respiratory Illness , Amer J Epidem , to be published.
Bleidner, W.E., et al:  Absorption, Distribution and Excretion of Amantadine Hydrochloride , J Pharmacol Exp Ther 150: 484-490 ( (Dec) ) 1965;.
Tyler, E.T., and Kessler, W.B.:  A Clinical Trial of Amantadine Hydrochloride Among Volunteers at the Family Planning Centers During the 1964 Rubella Epidemic in Los Angeles , read before the Symposium on Aspects of Antiviral Therapy at E. I. Du Pont de Nemours and Company, Wilmington, Del, Oct 22-23, 1964 .

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Davies, W.L., et al:  Antiviral Activity of 1-Adamantanamine . Science 144:862-863 ( (May 15) ) 1964;.
Neumayer, E.M.; Haff, R.F.; and Hoffman, C.E.:  Antiviral Activity of Amantadine Hydrochloride in Tissue Culture and in ovo , Proc Soc Exp Biol Med 119:393-396 ( (June) ) 1965;.
Hoffman, C.E., et al:  Mode of Action of the Antiviral Activity of Amantadine in Tissue Culture , J Bact 90:623-628 ( (Sept) ) 1965;.
Schild, G.C., and Sutton, E.N.P.:  Inhibition of Influenza Viruses in vitro and in vivo by 1-Adamantanamine Hydrochloride . Brit J Exp Path 46:263-273 ( (June) ) 1965;.
Cochran, K.W., et al:  Studies on the Antiviral Activity of Amantadine Hydrochloride , Ann NY Acad Sci 130:432-439 ( (July 30) ) 1965;.
Tyrrell, D.A.J.; Bynoe, M.L.; and Hoorn, B.:  Studies on the Antiviral Activity of 1-Adamantanamine , Brit J Exp Path 46:370-375 ( (Aug) ) 1965;.
Maassab, H.F., and Cochran, K.W.:  Rubella Virus: Inhibition in Vitro by Amantadine Hydrochloride , Science 145:1443-1444 ( (Sept 25) ) 1964;.
Cusumano, C.L., et al:  Effect of Amantadine Hydrochloride on Rubella Virus in Tissue Culture and in Ferrets , abstracted, Bact Proc , 1965;, p 119.
Plotkin, S.A.:  Inhibition of Rubella Virus by Amantadine , Arch Ges Virusforsch 16:438-442, 1965;.
Grunert, R.R.; McGahen, J.W.; and Davies, W.L.:  The in vivo Antiviral Activity of 1-Adamantanamine (Amantadine): I. Prophylactic and Therapeutic Activity Against Influenza Virus , Virology 26:262-269 ( (June) ) 1965;.
Jackson, G.G.; Muldoon, R.L.; and Akers, L.W.:  Serological Evidence for Prevention of Influenzal Infection in Volunteers by an Anti-Influenzal Drug Adamantanamine Hydrochloride , Antimicrob Agents Chemother 3:703-707, 1963;.
Hornick, R.B.; Togo, Y.; and Dawkins, A.T.:  Prophylactic Efficacy of Amantadine HCl in Volunteers With Experimentally Induced A2 Influenza Infection , abstracted; Bact Proc , 1966;, p 131.
Stanley, E.D., et al:  Evaluation of Antiviral Drugs: The Effect of Amantadine on Influenza in Volunteers , Ann NY Acad Sci 130:44-51 ( (July 30) ) 1965;.
Wendel, H.A.; Snyder, M.T.; and Pell, S.:  Trial of Amantadine in Epidemic Influenza , Clin Pharmacol Ther 7:38-43 ( (Jan) -Feb) 1966;.
Quilligan, J.J., Jr.; Hirayama, M.; and Baernstein, H.D., Jr.:  The Supression of A2 Influenza in Children by the Chemoprophylactic Use of Amantadine , J Pediat 69:572-575 ( (Oct) ) 1966;.
Finklea, J.T.; Hennessy, A.V.; and Davenport, F.M.:  A Field Trial of Amantadine Prophylaxis in Naturally Occurring Acute Respiratory Illness , Amer J Epidem , to be published.
Bleidner, W.E., et al:  Absorption, Distribution and Excretion of Amantadine Hydrochloride , J Pharmacol Exp Ther 150: 484-490 ( (Dec) ) 1965;.
Tyler, E.T., and Kessler, W.B.:  A Clinical Trial of Amantadine Hydrochloride Among Volunteers at the Family Planning Centers During the 1964 Rubella Epidemic in Los Angeles , read before the Symposium on Aspects of Antiviral Therapy at E. I. Du Pont de Nemours and Company, Wilmington, Del, Oct 22-23, 1964 .
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