Efficacy of Repeated Intravenous Administration of Peramivir against Highly Pathogenic Avian Influenza A (H5N1) Virus in Cynomolgus Macaques

Kitano, Mitsutaka; Itoh, Yasushi; Ishigaki, Hirohito; Nakayama, Misako; Ishida, Hideyuki; Pham, Van Loi; Arikata, Masahiko; Shichinohe, Shintaro; Tsuchiya, Hideaki; Kitagawa, Naoko; Kobayashi, Masanori; Yoshida, Ruriko; Sato, Akihiko; Le, Quynh Mai; Kawaoka, Yoshihiro; Ogasawara, Kunio

doi:10.1128/aac.02817-14

Cited by 19 publications

(20 citation statements)

References 33 publications

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“…The pulmonary edema likely aggravates the severity of hypoxemia at 6 dpi in HK483 mice. Lethal H5N1 viral infection could also produce a body weight loss of 25-30% at 5-7 dpi in mice, cats, ferrets, and macaques (2,22,36,39). In agreement, we found a loss of body weight (10 -25%) at 4 -6 dpi in this study.…”

Section: Discussionmentioning

confidence: 99%

Lethal avian influenza A (H5N1) virus induces ataxic breathing in mice with apoptosis of pre-Botzinger complex neurons expressing neurokinin-1 receptor

Zhuang

Zang

et al. 2017

American Journal of Physiology-Lung Cellular and Molecular Phys

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Lethal influenza A (H5N1) induces respiratory failure in humans. Although it also causes death at 7 days postinfection (dpi) in mice, the development of the respiratory failure and the viral impact on pre-Botzinger complex (PBC) neurons expressing neurokinin 1 receptor (NKR), which is the respiratory rhythm generator, have not been explored. Body temperature, weight, ventilation, and arterial blood pH and gases were measured at 0, 2, 4, and 6 dpi in control, lethal HK483, and nonlethal HK486 viral-infected mice. Immunoreactivities (IR) of PBC NKR, H5N1 viral nucleoprotein (NP), and active caspase-3 (CASP3; a marker for apoptosis) were detected at 6 dpi. HK483, but not HK486, mice showed the following abnormalities: ) gradual body weight loss and hypothermia;) tachypnea at 2-4 dpi and ataxic breathing with long-lasting apneas and hypercapnic hypoxemia at 6 dpi; and ) viral replication in PBC NKR neurons with NKR-IR reduced by 75% and CASP3-IR colabeled at 6 dpi. Lethal H5N1 viral infection causes tachypnea at the early stage and ataxic breathing and apneas (hypercapnic hypoxemia) leading to death at the late stage. Its replication in the PBC induces apoptosis of local NKR neurons, contributing to ataxic breathing and respiratory failure.

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Section: Discussionmentioning

confidence: 99%

Lethal avian influenza A (H5N1) virus induces ataxic breathing in mice with apoptosis of pre-Botzinger complex neurons expressing neurokinin-1 receptor

Zhuang

Zang

et al. 2017

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…The Chinese Food and Drug Administration announced the approval of peramivir for treatment in the H7N9 outbreak in China on 6 April 2013, with an expectation to save patients with severe symptoms. In addition, the United States Food and Drug Administration issued an emergency use authorization of intravenous peramivir exclusively for patients who were hospitalized for influenza A (H1N1) pdm09-associated infection on 23 October 2009 [27]. In this research, peramivir was selected as a positive drug.…”

Section: In Vitro Antiviral Evaluationmentioning

confidence: 99%

Geniposide Demonstrates Anti-Inflammatory and Antiviral Activity against Pandemic A/Jiangsu/1/2009 (H1N1) Influenza virus Infection in vitro and in vivo

Zhang

Yao

et al. 2016

Antiviral Therapy

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“…Hosoya et al most highly recommended the once-daily administration of 10 mg/kg of peramivir for 5 consecutive days in the official website of Japan Pediatric Society 98. In a macaque model infected with HPAIA (H5N1), repeated peramivir administration (30 mg/kg/day once a day for 5 days) starting immediately after infection significantly reduced viral titers in the upper respiratory tract ( P <0.05) 99. These results provide supportive evidence for the repeated administration of peramivir to highly pathogenic avian influenza virus infection.…”

Section: Resultsmentioning

confidence: 57%

Safety and efficacy of peramivir for influenza treatment

Hata¹,

Akashi-Ueda²,

Takamatsu³

et al. 2014

DDDT

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ObjectiveThis report presents a review of the efficacy and safety of peramivir, a neuraminidase inhibitor that was granted Emergency Use Authorization by the US Food and Drug Administration (FDA) from October 23, 2009 to June 23, 2010 during the 2009 H1N1 pandemic.MethodsLiterature was accessed via PubMed (January 2000–April 2014) using several search terms: peramivir; BCX-1812; RWJ 270201; H1N1, influenza; antivirals; and neuraminidase inhibitors. The peramivir manufacturers, Shionogi and Co Ltd and BioCryst Pharmaceuticals, were contacted to obtain unpublished data and information presented at recent scientific meetings. Information was obtained from the Centers for Disease Control and Prevention (CDC) and from US FDA websites. English-language and Japanese-language reports in the literature were reviewed and selected based on relevance, along with information from the CDC, US FDA, and the drug manufacturers.ResultsWe obtained eleven clinical trial reports of intravenous peramivir, two of which described comparisons with oseltamivir. Seven of nine other recently reported published studies was a dose–response study. Clinical reports of critically ill patients and pediatric patients infected with pandemic H1N1 described that early treatment significantly decreased mortality. Peramivir administered at 300 mg once daily in adult patients with influenza significantly reduces the time to alleviation of symptoms or fever compared to placebo. It is likely to be as effective as other neuraminidase inhibitors.ConclusionAlthough peramivir shows efficacy for the treatment of seasonal and pH1N1 influenza, it has not received US FDA approval. Peramivir is used safely and efficiently in hospitalized adult and pediatric patients with suspected or laboratory-confirmed influenza. Peramivir might be a beneficial alternative antiviral treatment for many patients, including those unable to receive inhaled or oral neuraminidase inhibitors, or those requiring nonintravenous drug delivery.

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Efficacy of Repeated Intravenous Administration of Peramivir against Highly Pathogenic Avian Influenza A (H5N1) Virus in Cynomolgus Macaques

Cited by 19 publications

References 33 publications

Lethal avian influenza A (H5N1) virus induces ataxic breathing in mice with apoptosis of pre-Botzinger complex neurons expressing neurokinin-1 receptor

Lethal avian influenza A (H5N1) virus induces ataxic breathing in mice with apoptosis of pre-Botzinger complex neurons expressing neurokinin-1 receptor

Geniposide Demonstrates Anti-Inflammatory and Antiviral Activity against Pandemic A/Jiangsu/1/2009 (H1N1) Influenza virus Infection in vitro and in vivo

Safety and efficacy of peramivir for influenza treatment

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