Bemnifosbuvir

Bemnifosbuvir is a novel phosphoramidate prodrug of 2'-fluoro-2'-C-methylguanosine-5'-monophosphate that has potent in vitro activity against HCV.(In Vitro):AT-511 is a novel phosphoramidate prodrug of 2'-fluoro-2'-C-methylguanosine-5'-monophosphate that has potent in vitro activity against HCV.In the absence of cells, AT-511 was stable when incubated in culture medium at 37°C for up to 24 h. AT-9010 was the predominant intracellular metabolite measured in all hepatocyte species and Huh-7 cell incubations with 10 μM AT-511 and, except in mouse hepatocytes,far exceeded intracellular AT-511 concentrations,demonstrating that the active TP was efficiently formed from its phosphoramidate protide in liver cells. In hepatocyte incubations, the relative levels of AT-9010 formed, and its accumulation over 24 h expressed as area under the curve or AUC0-24h; from most to least abundant, were rat>human >mouse >dog/monkey.(In Vivo):Treatment with moxifloxacin every 8 hr was accompanied by longer survival than in any other group.Tissue cultures 30 hr after bacterial challenge showed considerably less bacterial growth in the spleens and lungs of moxifloxacin-treated animals than in the other groups, but not in their livers.