Efficacy of delayed treatment of China-made Peramivir with repeated intravenous injections in a mouse influenza model: from clinical experience to basal experiment

BMC Infect Dis. 2016 Jul 8:16:325. doi: 10.1186/s12879-016-1589-9.

Abstract

Background: China-made Peramivir, an anti-influenza neuraminidase inhibitor drug, is manufactured and widely used in China. Although effective if initiated within 48 h of the onset of symptoms, yet we observed that this drug shows an inconclusive efficacy if treatment is delayed in clinical. Thus we evaluated the efficacy of delayed treatment of China-made Peramivir in a mouse model.

Methods: The mouse model of influenza infection was made and Peramivir was administered intravenously for 5 days following infection, and weight loss, lung index, viral shedding and survival rates were monitored.

Results: Peramivir (60 mg/kg · d, repeated intravenous injections, quaque die (QD) × 5 days) enhanced survival rate and suppressed weight loss when treatment was initiated 24, 36, 48, or even 60 h post-infection (p.i.) (p < 0.01), compared with the virus-untreated group, and efficacy was abolished at 72 h p.i.. However the efficacy of delayed treatment was dose dependent, with the highest dose (90 mg/kg · d) even showing efficacy at 72 h p.i.. Furthermore, Peramivir (60 mg/kg · d, repeated intravenous injections, QD × 5 days) also reduced the lung virus titer 24 and 36 h p.i. on day 5, and even at 48 and 60 h p.i. on day 7 after infection, and the lung index was also improved. What is interesting that the concentration of the drug was maintained in blood after infected.

Conclusions: Delayed treatment with China-made Peramivir can reduce the severity of influenza disease, accelerate viral clearance and enhance the survival rate. This drug therefore shows good efficacy and is a promising candidate to control the influenza epidemic in China.

Keywords: Delayed treatment; Lung index; Lung virus titer; Peramivir; Survival rate.

MeSH terms

  • Acids, Carbocyclic
  • Administration, Intravenous
  • Animals
  • Antiviral Agents / administration & dosage*
  • China
  • Cyclopentanes / administration & dosage*
  • Disease Models, Animal
  • Drug Administration Schedule
  • Female
  • Guanidines / administration & dosage*
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Injections, Intravenous
  • Lung / virology
  • Male
  • Mice
  • Orthomyxoviridae Infections / drug therapy*
  • Viral Load / drug effects
  • Virus Shedding / drug effects

Substances

  • Acids, Carbocyclic
  • Antiviral Agents
  • Cyclopentanes
  • Guanidines
  • peramivir