Ribavirin Small-Particle Aerosol Treatment of Influenza

Knight, Vernon; Wilson, Samuel Z.; Quarles, John; Greggs, SharonE.; McClung, H W; Waters, BarryK.; Cameron, RobertW.; Zerwas, JohnM.; Couch, R B

doi:10.1016/s0140-6736(81)91152-1

Cited by 198 publications

(118 citation statements)

References 18 publications

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“…59 -60 Several small, uncontrolled studies, primarily ones involving healthy adult patients with uncomplicated influenza A and B infections, have reported some therapeutic benefit when ribavirin is administered via aerosol for Ͼ 12 hours per day, especially if treatment is initiated early (i.e., before the onset of respiratory failure). [61][62][63] The idea of combination antiviral therapy for treatment of severe influenza infections also has been proposed but has not been explored in any controlled trials. Compared with single agents, combinations of ribavirin with amantadine or rimantadine showed enhanced antiviral activity in vitro and in animal models of influenza A infection.…”

Section: Treatment Of Severe Influenza Infectionsmentioning

confidence: 99%

Common community respiratory viruses in patients with cancer

Hicks

Chemaly

Kontoyiannis

2003

Cancer

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Section: Treatment Of Severe Influenza Infectionsmentioning

confidence: 99%

Common community respiratory viruses in patients with cancer

Hicks

Chemaly

Kontoyiannis

2003

Cancer

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“…Ribavirin, a broad spectrum antiviral agent Witkowski et al, 1972;Huffman et al, 1973;Oxford 1975), has been considered for use against influenza A and B viruses. Ribavirin, given by aerosol treatment, had a therapeutic effect as evidenced by reduction in systemic illness and elimination of influenza A virus from respiratory secretions in 14 randomly selected college students infected with the virus (Knight et al, 1981). Furthermore, in a randomized, controlled study, 11 students infected with influenza B virus and treated with aerosolized ribavirin, experienced reduction in systemic illness and reduced virus shedding in nasal secretions with minimal adverse effects (McClung et al, 1983).…”

Section: Introductionmentioning

confidence: 99%

Cellular Metabolism and Anti-Influenza Activity of 1,3,4-Thiadiazol-2-Ylcyanamide (LY217896)

Colacino

Birch

Tang

1993

Antivir Chem Chemother

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LY217896 (1,3,4-thiadiazol-2-ylcyanamide) is a 2-substituted thiadiazole that is an effective inhibitor of influenza A and B viruses in vitro and in the mouse infection model. The in vitro anti-influenza activity of LY217896 is reversed by a 10-fold excess amount of guanine or guanosine. LY217896 (1 or 10μg ml−1) effected a selective 60% decrease in the levels of intracellular pools of GTP in MDCK cells. The extent of cytotoxicity of LY217896 is positively correlated with the amount of LY217896 metabolite formed intracellularly. A cell line, derived from parental MDCK cells, was selected for resistance to 50 ng of LY217896 per ml. Unlike parental MDCK cells, the resistant cells were able to undergo log phase replication in LY217896 (25 g ml−1) and were unable to metabolize the compound. Furthermore, LY217896 had no antiviral activity against influenza A/Ann Arbor (IC50 >200μg ml−1) or vaccinia virus (IC50 = 13 μg ml−1) in resistant cells. In contrast, LY217896 inhibited influenza A/Ann Arbor (IC50 = 0.5 μg ml−1) or vaccinia virus (IC50 = 0.13 μg ml−1) in the parental MDCK cells. A thiadiazole, with a guanidinyl group in the 2 position, and ribavirin were active in both the parental cells and resistant cells. Nicotinamide (up to 240-fold excess) did not reverse the anti-influenza activity of LY217896 in vitro or in the mouse infection model. A 10-fold excess of nicotinamide reversed the cytotoxicity of 2-aminothiadiazole but not that of LY217896.

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“…or exposed to a continuous SPA of one of these materials for 8 h ( Table 1.) The aerosol generators and their use to deliver interferons (23) or other antiviral agents (12,13,22) have been described previously. In these experiments, rIFN alpha A/D was diluted in sterile saline (0.9% sodium chloride no.…”

Section: Methodsmentioning

confidence: 99%

Duration of effect of interferon aerosol prophylaxis of vesicular stomatitis virus infection in mice

Wyde¹,

Sun²,

Wilson³

et al. 1985

Antimicrob Agents Chemother

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Mice were exposed for 8 h to continuous small-particle aerosols containing natural mouse alpha interferon (estimated dosage 100 U per mouse) or one of two concentrations of hybrid recombinant alpha interferon A/D bgl (estimated dosages of 100 and 10,000 U per mouse, respectively). On days 1, 3, 5, 7, and 9 after exposure to these interferons, three mice from each group were inoculated intranasally with 100 PFU of vesicular stomatitis virus. Control mice were exposed to aerosols of saline or inoculated intraperitoneally with either natural mouse alpha interferon (350 U) or one of two doses of hybrid recombinant alpha interferon A/D bgl (350 or 35,000 U) and challenged similarly. Of mice injected intraperitoneally, only those given 35,000 U of hybrid recombinant alpha interferon A/D bgl 24 h before virus challenge were protected from pulmonary infection, compared with the saline-treated control mice. Of mice given 100 U of either interferon by small-particle aerosol, only those exposed 24 h before inoculation of vesicular stomatitis virus had reduced pulmonary titers of the virus. However, of mice given ca. 10,000 U of hybrid recombinant alpha interferon A/D bgl by small-particle aerosol, all groups except those exposed 9 days before virus inoculation had significantly reduced lung virus titers.

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Ribavirin Small-Particle Aerosol Treatment of Influenza

Cited by 198 publications

References 18 publications

Common community respiratory viruses in patients with cancer

Common community respiratory viruses in patients with cancer

Cellular Metabolism and Anti-Influenza Activity of 1,3,4-Thiadiazol-2-Ylcyanamide (LY217896)

Duration of effect of interferon aerosol prophylaxis of vesicular stomatitis virus infection in mice

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