Protection of Man from Natural Infection with Influenza A2 Hong Kong Virus by Amantadine: A Controlled Field Trial

Oker-Blom, N; Hovi, Tapani; Leinikki, Pauli; Palosuo, Timo; Pettersson, Ralf F.; Suni, Jukka

doi:10.1136/bmj.3.5724.676

Cited by 51 publications

(22 citation statements)

References 15 publications

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“…When drugs are added before infection at concentrations ranging from 0.5 to 2 ,ug/ml, rimantadine is more effective than amantadine. These levels are comparable to the levels achieved in sera after oral administration of 200 mg of amantadine per day to humans (9), a dose regimen which has been shown to be effective for prophylaxis against influenza (22,24,25,27). Furthermore, rimantadine produced protection against CPE roughly equal to the protection produced by 0.5 to 1 ,ug of amantadine per ml at eightfold-lower concentrations.…”

Section: Discussionsupporting

confidence: 59%

“…Amantadine hydrochloride has been evaluated widely as a chemoprophylactic agent against influenza A virus (6,17,18) and has established efficacy for preventing or modifying disease (22,24,25,27). As a therapeutic agent, amantadine hastens resolution of uncomplicated influenza (8,36), but in established influenza pneumonia less impressive results have been observed (7).…”

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confidence: 99%

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Anti-influenza A virus activity of amantadine hydrochloride and rimantadine hydrochloride in ferret tracheal ciliated epithelium

Meiklejohn¹,

Mostow²

1982

Antimicrob Agents Chemother

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The activities and toxicities of amantadine hydrochloride and rimantadine hydrochloride against influenza A/Alaska/6/77 (H3N2) and A/Bangkok/l/79 (H3N2) viruses were compared in organ cultures of ferret tracheal ciliated epithelium. Pretreatment of cultures with concentrations (0.5 and 1 ,ug/ml) comparable to those found in human serum after oral administration of amantadine revealed that rimantadine produced significantly longer protection than amantadine against virus-induced cytopathic effects. Correspondingly, rimantadine produced a comparable protective effect at four-to eight-fold-lower concentrations than amantadine. Both drugs produced increasing and similar effects at higher concentrations, which were comparable to those reported in nasal washings after aerosol administration of amantadine. At the concentrations tested, amantadine was nontoxic. However, at concentrations of 16 and 32 ,ug/ml, rimantadine was toxic to the ciliated epithelium after 10 to 21 days of continuous exposure. When the drugs were added 24 h or more after infection, protection against cytopathic effects decreased markedly. Both drugs moderately suppressed virus production at concentrations of 0.5 to 16 ,ug/ml. However, no dose response or difference between the drugs was observed. Because of comparable antiviral activity at lower concentrations and greater activity at similar concentrations, rimantadine may be more useful than amantadine for oral prophylaxis and therapy of influenza.

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Section: Discussionsupporting

confidence: 59%

mentioning

confidence: 99%

Anti-influenza A virus activity of amantadine hydrochloride and rimantadine hydrochloride in ferret tracheal ciliated epithelium

Meiklejohn¹,

Mostow²

1982

Antimicrob Agents Chemother

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“…Although vaccines are the best means of protection, antivirals constitute an important modality for the control of these infections. The adamantanes, also called M2 ion channel blockers, have been available for the treatment and prevention of influenza infections for the past 40 years (13). Since 2005Since -2006, however, the widespread emergence of the S31N mutation in the M2 gene conferring adamantane resistance has greatly reduced the usefulness of these agents in treating A/H3N2 viruses (20).…”

mentioning

confidence: 99%

The I222V Neuraminidase Mutation Has a Compensatory Role in Replication of an Oseltamivir-Resistant Influenza Virus A/H3N2 E119V Mutant

et al. 2011

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“…Both drugs are very effective in preventing illness due to influenza A virus. When given prophylactically during a community outbreak, either compound reduces the risk of acquiring influenzal illness by 50 to 90% ( 68,110,161,317,331,500). Rimantadine has fewer side effects when used in NH2 HCI this manner, although lowering the dose of amantadine also reduces adverse effects (378,419).…”

Section: Antiviral Agents Amantadine and Rimantadinementioning

confidence: 99%

Antiviral therapy: current concepts and practices

Bean

1992

Clin Microbiol Rev

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Drugs capable of inhibiting viruses in vitro were described in the 1950s, but real progress was not made until the 1970s, when agents capable of inhibiting virus-specific enzymes were first identified. The last decade has seen rapid progress in both our understanding of antiviral therapy and the number of antiviral agents on the market. Amantadine and ribavirin are available for treatment of viral respiratory infections. Vidarabine, acyclovir, ganciclovir, and foscarnet are used for systemic treatment of herpesvirus infections, while ophthalmic preparations of idoxuridine, trifluorothymidine, and vidarabine are available for herpes keratitis. For treatment of human immunodeficiency virus infections, zidovudine and didanosine are used. Immunomodulators, such as interferons and colony-stimulating factors, and immunoglobulins are being used increasingly for viral illnesses. While resistance to antiviral drugs has been seen, especially among AIDS patients, it has not become widespread and is being intensely studied. Increasingly, combinations of agents are being used: to achieve synergistic inhibition of viruses, to delay or prevent resistance, and to decrease dosages of toxic drugs. New approaches, such as liposomes carrying antiviral drugs and computer-aided drug design, are exciting and promising prospects for the future.

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Protection of Man from Natural Infection with Influenza A2 Hong Kong Virus by Amantadine: A Controlled Field Trial

Cited by 51 publications

References 15 publications

Anti-influenza A virus activity of amantadine hydrochloride and rimantadine hydrochloride in ferret tracheal ciliated epithelium

Anti-influenza A virus activity of amantadine hydrochloride and rimantadine hydrochloride in ferret tracheal ciliated epithelium

The I222V Neuraminidase Mutation Has a Compensatory Role in Replication of an Oseltamivir-Resistant Influenza Virus A/H3N2 E119V Mutant

Antiviral therapy: current concepts and practices

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