Aerosol administration increases the efficacy of oseltamivir for the treatment of mice infected with influenza viruses

Leyva-Grado, Victor H.; Palese, Peter

doi:10.1016/j.antiviral.2017.03.002

Cited by 9 publications

(7 citation statements)

References 23 publications

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“…Our results are congruent with other reports showing that oral oseltamivir delivery is less efficacious than aerosolized oseltamivir. Notably, Leyva-Grado and colleagues compared several routes of administration of oseltamivir, and found that aerosolized oseltamivir given 24 h after infection confers protection against several strains of influenza, while oral oseltamivir protection was strain-specific and achieved at high doses only (Leyva-Grado 2017). Other reports indicate that oral oseltamivir may be efficacious at lower viral titers (Marjuki 2014) for extended treatment periods (Byrn 2015, Smee 2016,).…”

Section: Discussionmentioning

confidence: 99%

Combined aerosolized Toll-like receptor ligands are an effective therapeutic agent against influenza pneumonia when co-administered with oseltamivir

Leiva‐Juárez

Kirkpatrick

Gilbert

et al. 2018

European Journal of Pharmacology

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Influenza pneumonia remains a common and debilitating viral infection despite vaccination programs and antiviral agents developed for prophylaxis and treatment. The neuraminidase inhibitor oseltamivir is frequently prescribed for established influenza A virus infections, but the emergence of neuraminidase inhibitor resistant viruses, a brief therapeutic window and competing diagnoses complicate its use. PUL-042 is a clinical stage, aerosol drug comprised of synthetic ligands for Toll-like receptor (TLR) 2/6 and TLR 9. This host-targeted, innate immune stimulant broadly protects against bacterial, fungal and viral pneumonias, including those caused by influenza, when given prophylactically to animals. This study evaluated the therapeutic antiviral effects of PUL-042 against established influenza A pneumonia, when given alone or in combination with oseltamivir. Mice were treated with PUL-042 aerosol, oseltamivir or both at varying time points before or after challenge with influenza pneumonia. Treating established, otherwise lethal influenza A pneumonia (>1 LD) with multiple inhaled doses of PUL-042 aerosol plus oral oseltamivir resulted in greater mouse survival than treatment with either drug alone. Single agent PUL-042 also protected mice against established infections following challenges with lower viral inocula (approximately 1 LD). Aerosolized oseltamivir further enhanced survival when co-delivered with PUL-042 aerosol. The prophylactic and therapeutic benefits of PUL-042 were similar against multiple strains of influenza virus. In vitro influenza challenge of human HBEC3kt lung epithelial cells revealed PUL-042-induced protection against infection that was comparable to that observed in vivo. These studies offer new insights into means to protect susceptible populations against influenza A pneumonia.

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Section: Discussionmentioning

confidence: 99%

Combined aerosolized Toll-like receptor ligands are an effective therapeutic agent against influenza pneumonia when co-administered with oseltamivir

Leiva‐Juárez

Kirkpatrick

Gilbert

et al. 2018

European Journal of Pharmacology

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“…Oseltamivir) that block viral egress to potentially ameliorate disease are currently in use. Despite considerable efficacy in murine models in lowering viral titers and improving disease outcome [143,144], its protective effect in humans is controversial and limited benefit has been shown in the majority of patients [145,146]. Additionally, highly resistant strains of IAV to Oseltamivir have recently emerged that raises growing concern [147].…”

Section: Targeting Cell Death Programs As a Potential Therapy?mentioning

confidence: 99%

Dissecting host cell death programs in the pathogenesis of influenza

Downey

Pernet

François

et al. 2018

Microbes and Infection

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Influenza A virus (IAV) is a pulmonary pathogen, responsible for significant yearly morbidity and mortality. Due to the absence of highly effective antiviral therapies and vaccine, as well as the constant threat of an emerging pandemic strain, there is considerable need to better understand the host-pathogen interactions and the factors that dictate a protective versus detrimental immune response to IAV. Even though evidence of IAV-induced cell death in human pulmonary epithelial and immune cells has been observed for almost a century, very little is known about the consequences of cell death on viral pathogenesis. Recent study indicates that both the type of cell death program and its kinetics have major implications on host defense and survival. In this review, we discuss advances in our understanding of cell death programs during influenza virus infection, in hopes of fostering new areas of investigation for targeted clinical intervention.

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“…Oseltamivir como profilaxia da gripe [50], [51]. A nitazoxanida é relatada, na literatura, como um novo candidato a fármaco para o tratamento do coronavírus da síndrome respiratória do Oriente Médio [52].…”

Section: Histogramas Dos Nebulizadoresunclassified

Engenharia biomédica: uma abordagem holística

2021

Engenharia Biomédica: Uma Abordagem Holística

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Atualmente, vários medicamentos estão sendo usados de forma sistêmica para o tratamento da Síndrome Respiratória Aguda Grave Coronavírus 2 (SARS-CoV-2). No entanto, poucos estudos discutem a possibilidade de utilizar a via inalatória para esse fim. Os nebulizadores pneumáticos e ultrassônicos são cada vez mais utilizados devido à facilidade com que esses meios entregam os medicamentos por meio de uma suspensão em aerossol para dispensar os medicamentos de forma localizada no trato respiratório, proporcionando maior eficiência de absorção. Este estudo tem como objetivo caracterizar os diâmetros das gotas por faixas de "partículas respiráveis" geradas por nebulizadores comercializados no Brasil (2 pneumáticos e 1 ultrassônico), utilizando a técnica de incidência laminar direta (ILD). Além disso, discutir o uso de medicamentos por inalação com base nas propriedades físico-químicas e farmacológicas. No procedimento de nebulização, as imagens das gotículas aerodinâmicas dispersas foram capturadas usando a técnica ILD. Foram elaborados histogramas de distribuição do diâmetro das gotas, enfatizando a faixa de gotas com diâmetros entre 1,0 a 5,0 µm. Os resultados atestaram que cada nebulizador tem sua própria característica de entregar a suspensão aerodinâmica no processo de nebulização. Neste estudo, o ILD representa uma alternativa viável para caracterização das gotículas aero dispersas, de fármacos usados mundialmente para o tratamento de sinais e sintomas da SARS-CoV-2.

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Aerosol administration increases the efficacy of oseltamivir for the treatment of mice infected with influenza viruses

Cited by 9 publications

References 23 publications

Combined aerosolized Toll-like receptor ligands are an effective therapeutic agent against influenza pneumonia when co-administered with oseltamivir

Combined aerosolized Toll-like receptor ligands are an effective therapeutic agent against influenza pneumonia when co-administered with oseltamivir

Dissecting host cell death programs in the pathogenesis of influenza

Engenharia biomédica: uma abordagem holística

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