Influence of virus strain, challenge dose, and time of therapy initiation on the in vivo influenza inhibitory effects of RWJ-270201.

摘要: The influenza virus neuraminidase inhibitor RWJ-270201 (cyclopentane carboxylic acid, 3-[cis-1-(acetylamino)-2-ethylbutyl]-4[(aminoiminomethyl)amino]-2-hydroxy-[cis, 2S, 3R, 4R]) was significantly inhibitory to an infection in mice induced by A/NWS/33 (H1N1) when oral gavage (p.o.) treatment with 10 mg/kg per day delayed at least 60 h after exposure. Treatment 5 twice daily for days. Viral challenge doses of A/Shangdong/09/93 (H3N2) ranging from the LD(70) LD(100) did not affect marked antiviral efficacy 12.5 administered p.o. days beginning 4 pre-virus exposure; approximate 2 dose (10(8) cell culture infectious doses/ml) only weakly inhibited same as seen significant increase mean death. Murine infections A/Bayern/57/93 and B/Lee/40 viruses were 100, 10, 1 using above regimen; A/PR/8/34 moderately inhibited, effects this being lessening arterial oxygen decline, reduced lung consolidation, inhibition titers primarily higher dosages.