The hepatitis C virus (HCV) NS3/4A protease is a trypsin-like serine protease, which is essential for the generation of components of the viral RNA replication complex. Simeprevir is a single pill, oral HCV NS3/4A protease inhibitor, currently approved for the treatment of patients with HCV genotype 1 infection. Simeprevir exhibits potent inhibition of NS3/4A protease of genotypes 1a, 1b, 2, 4, 5, and 6, with IC50 <13 nM for all HCV NS3/4A enzymes. In replicon models, different genotype 1a and 1b replicons showed EC50 for simeprevir ranging from 8 nM to 28 nM. In vivo, simeprevir had a relatively long absorption phase, reaching maximum concentration (Cmax) after 4–6 hours. Moreover, simeprevir was extensively (99.9%) bound to plasma proteins, mainly to albumin. The absolute bioavailability was 44% after a single oral administration[3].
搜索
