TABLE 3.

Effect of four-times-daily treatmenta with T-705 or oseltamivir on an infection in mice induced by influenza A/Duck/MN/1525/81 (H5N1) virus

Expt no. and treatmentaDose (mg/kg/day)Infected, treated micegToxicity controls
No. of survivors/total no. testedMDDb ± SDDay 1 mean lung virus titerc ± SDDay 6 mean lung scored ± SDDay 6 mean lung wt (mg) ± SDMean day 11 SaO2 (%) ± SDNo. of survivors/total no. tested following rechallengeeNo. of survivors/total no. testedMean host wt changef (g)
Expt 1
    T-70530010/10***>21.0***3.5 ± 0.8***0.3 ± 0.3*146 ± 12***88.6 ± 3.8***10/103/30.6
    T-70510010/10***>21.0***4.9 ± 0.3**0.5 ± 0.0*140 ± 20***85.9 ± 5.9***10/103/31.1
    T-7053310/10***>21.0***5.8 ± 0.51.3 ± 0.3*217 ± 6**84.8 ± 4.8***10/103/30.2
    Oseltamivir202/109.4 ± 1.2***6.1 ± 0.52.2 ± 0.6*270 ± 36*76.9 ± 3.8*0/23/30.6
    CMC0/206.6 ± 1.16.3 ± 0.43.3 ± 0.3360 ± 4275.0 ± 0.0
    Healthy controls0.0 ± 0.00.0 ± 0.0117 ± 2192.6 ± 3.50/53/30.8
Expt 2
    T-7053009/9***>21.0***2.4 ± 0.4***0.5 ± 0.0*123 ± 15***85.9 ± 6.9***9/93/30.0
    T-70510010/10***>21.0***5.3 ± 0.3**0.7 ± 0.3*153 ± 15***84.6 ± 4.4***10/103/3−0.1
    T-705339/10***12.0 ± 0.05.8 ± 0.41.7 ± 0.6*173 ± 6***81.6 ± 6.3***9/93/30.0
    Oseltamivir201/109.3 ± 1.7***6.3 ± 0.13.5 ± 0.0247 ± 23**76.6 ± 3.91/13/30.2
    CMC0/206.1 ± 0.86.4 ± 0.43.6 ± 0.2328 ± 1375.0 ± 0.0
    Healthy controls5/5>21.00.0 ± 0.00.0 ± 0.0117 ± 693.2 ± 2.80/53/31.3
  • a The doses were administered every 6 h for 5 days beginning 1 h after virus exposure (oseltamivir was given twice daily for 5 days beginning 1 h after virus exposure).

  • b MDD, mean day to death of mice dying prior to day 21.

  • c Log10 CCID50/g.

  • d Plum coloration of lung ranging from 0 (normal lung) to 4 (maximal coloration).

  • e Rechallenged with 100-fold more virus on day 21.

  • f Difference between initial weight and weight 18 h after final treatment.

  • g *, P < 0.05 compared to the results for the CMC-treated controls; **, P < 0.01 compared to the results for the CMC-treated controls; ***, P < 0.001 compared to the results for the CMC-treated controls.