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Antiviral Agents

Therapeutic Activity of Intramuscular Peramivir in Mice Infected with a Recombinant Influenza A/WSN/33 (H1N1) Virus Containing the H275Y Neuraminidase Mutation

Yacine Abed, Andrés Pizzorno, Guy Boivin
Yacine Abed
Research Center in Infectious Diseases of the CHUQ-CHUL and Laval University, Quebec City, Quebec, Canada
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Andrés Pizzorno
Research Center in Infectious Diseases of the CHUQ-CHUL and Laval University, Quebec City, Quebec, Canada
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Guy Boivin
Research Center in Infectious Diseases of the CHUQ-CHUL and Laval University, Quebec City, Quebec, Canada
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DOI: 10.1128/AAC.00753-12
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    Fig 1

    Impact of NAI regimens, starting at 24 h (A) or 48 h (B) after viral challenge, on body weight loss in mice infected with 6.9 × 103 PFU (A) or 8 × 103 PFU (B) of the recombinant A/WSN/33 (H1N1) WT virus. Regimens consisted of a single dose (90 mg/kg) or multiple doses (5 × 45 mg/kg, once daily [q.d.]) of IM peramivir (Per) and low-dose (1 mg/kg, q.d.) or high-dose (10 mg/kg, q.d.) oral oseltamivir (Osel). Each symbol represents the mean weight gain or loss of 12 mice ± standard deviation (SD).

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    Fig 2

    Impact of NAI regimens starting at 24 h (A) or 48 h (B) after viral challenge on body weight loss in mice infected with 5.7 × 103 PFU of the recombinant A/WSN/33 (H1N1) H275Y NA mutant. Regimens consisted of a single dose (90 mg/kg) or multiple doses (5 × 45 mg/kg, q.d.) of IM peramivir and low-dose (1 mg/kg, q.d.) or high-dose (10 mg/kg, q.d.) oral oseltamivir. Each symbol represents the mean weight gain or loss of 12 mice ± SD.

Tables

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  • Table 1

    Impact of NAI therapy starting at 24 h postinfection in mice infected with a recombinant A/WSN/33 (H1N1) WT virusa

    Regimen% mortality on day 12 p.i. (n = 8)Mean % wt loss ± SD on day 5 p.i. (n = 11–12)Mean lung viral titer (PFU/ml) ± SD on day 5 p.i. (n = 4)
    Uninfected/untreated0***−3.5 ± 0.7***Nd
    Untreated-infected7515.6 ± 1.52.85 × 105 ± 0.1 × 105
    Oseltamivir 5 × 1 mg/kg0***7.2 ± 1.2**1.3 × 102 ± 0.65 × 102***
    Peramivir 1 × 90 mg/kg0***−2.5 ± 0.9***4 × 101 ± 1 × 101***
    Peramivir 5 × 45 mg/kg0***−2.6 ± 1.1***0.66 × 101 ± 0.11 × 101***
    • ↵a **, P < 0.01; ***, P < 0.001 (versus the untreated group). Statistical significance was determined by using Kaplan-Meier analysis for mortality and a one-way ANOVA test for weight loss and lung viral titers. Nd, not determined. The viral inoculum was 6.9 × 103 PFU.

  • Table 2

    Impact of NAI therapy starting at 48 h postinfection in mice infected with a recombinant A/WSN/33 (H1N1) WT virusa

    Regimen% mortality on day 12 p.i. (n = 8)Mean % wt loss ± SD on day 5 p.i. (n = 11–12)Mean lung viral titer (PFU/ml) ± SD on day 5 p.i. (n = 4)
    Uninfected/untreated0***−2.8 ± 0.7***Nd
    Untreated-infected10020.4 ± 1.11.6 × 106 ± 0.6 × 106
    Oseltamivir 5 × 1 mg/kg0***5.3 ± 0.8***6.6 × 101 ± 6.4 × 101***
    Oseltamivir 5 × 10 mg/kg0***4.4 ± 1***8.6 × 101 ± 4.6 × 101***
    Peramivir 1 × 90 mg/kg0***1.5 ± 0.7***2 × 101 ± 0***
    Peramivir 5 × 45 mg/kg0***2 ± 0.8***2 × 101 ± 0***
    • ↵a ***, P < 0.001 versus the untreated group. Statistical significance was determined by using Kaplan Meier analysis for mortality and the one-way ANOVA test for weight loss and lung viral titers. Nd, not determined. The viral inoculum was 8 × 103 PFU.

  • Table 3

    Impact of NAI therapy starting at 24 h postinfection in mice infected with a recombinant A/WSN/33 (H1N1) H275Y virusa

    Regimen% mortality on day 12 p.i. (n = 8)Mean % wt loss ± SD on day 5 p.i. (n = 11–12)Mean lung viral titer (PFU/ml) ± SD on day 5 p.i. (n = 4)
    Uninfected/untreated0***−1.2 ± 1.1***Nd
    Untreated-infected7516.9 ± 1.53.66 × 106 ± 0.11 × 106
    Oselamivir 5 × 1 mg/kg7514 ± 1.43.0 × 106 ± 0.09 × 106
    Oseltamivir 5 × 10 mg/kg0***11.9 ± 1*2.0 × 105 ± 0.44 × 105***
    Peramivir 1 × 90 mg/kg0***−0.6 ± 0.9***8.0 × 102 ± 5.29 × 102***
    Peramivir 5 × 45 mg/kg0***−1.3 ± 1.1***2.2 × 103 ± 0.6 × 103***
    • ↵a *, P < 0.05; ***, P < 0.001 (versus the untreated group). Statistical significance was determined by using Kaplan-Meier analysis for mortality and the one-way ANOVA test for weight loss and lung viral titers. Nd, not determined. The viral inoculum was 5.7 × 103 PFU.

  • Table 4

    Impact of NAI therapy starting at 48 h postinfection in mice infected with a recombinant A/WSN/33 (H1N1) H275Y virusa

    Regimen% mortality on day 12 p.i. (n = 8)% wt loss ± SD on day 5 p.i. (n = 11–12)Mean lung viral titer (PFU/ml) ± SD on day 5 p.i. (n = 4)
    Uninfected/untreated0***−1.2 ± 1.1***Nd
    Untreated/infected7516.9 ± 1.53.66 × 106 ± 0.11 × 106
    Oseltamivir 5 × 1 mg/kg10018.3 ± 0.72.2 × 106 ± 0.52 × 106
    Oseltamivir 5 × 10 mg/kg62.516.5 ± 1.51.46 × 106 ± 0.41 × 106
    Peramivir 1 × 90 mg/kg0***7.9 ± 0.9***2.8 × 104 ± 0.7 × 104*
    Peramivir 5 × 45 mg/kg0***9.4 ± 1.4**3 × 103 ± 1.8 × 103***
    • ↵a *, P < 0.05; **, P < 0.01; ***, P < 0.001 (versus the untreated group). Statistical significance was determined by using Kaplan-Meier analysis for mortality and the one-way ANOVA test for weight loss and viral lung titers. Nd, not determined. The viral inoculum was 5.7 × 103 PFU.

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Therapeutic Activity of Intramuscular Peramivir in Mice Infected with a Recombinant Influenza A/WSN/33 (H1N1) Virus Containing the H275Y Neuraminidase Mutation
Yacine Abed, Andrés Pizzorno, Guy Boivin
Antimicrobial Agents and Chemotherapy Jul 2012, 56 (8) 4375-4380; DOI: 10.1128/AAC.00753-12

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Therapeutic Activity of Intramuscular Peramivir in Mice Infected with a Recombinant Influenza A/WSN/33 (H1N1) Virus Containing the H275Y Neuraminidase Mutation
Yacine Abed, Andrés Pizzorno, Guy Boivin
Antimicrobial Agents and Chemotherapy Jul 2012, 56 (8) 4375-4380; DOI: 10.1128/AAC.00753-12
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