生物活性

TMC435350 (Simeprevir) is an oral HCV NS3/4A protease inhibitor. TMC435350 inhibited HCV replication in a cellular assay (subgenomic 1b replicon) with a half-maximal effective concentration (EC(50)) of 8 nM and a selectivity index of 5,875. In rats, TMC435350 was extensively distributed to the liver and intestinal tract (tissue/plasma area under the concentration-time curve ratios of >35), and the absolute bioavailability was 44% after a single oral administration. TMC435350 also displayed low in vitro clearance and high permeability, which were confirmed by in vivo pharmacokinetic studies. Data from phase I and II clinical trials of TMC-435350 (Simeprevir) have shown that TMC435350 is well tolerated as a once-daily oral therapy and provides potent antiviral activity in HCV genotype 1-infected subjects, with restoration of liver enzymes and no evidence of viral breakthrough.

化学数据

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。

储备液配制

以下数据基于产品分子量，对于特殊产品，请参照COA中的储备液配制条件和说明进行操作。