Paritaprevir (ABT-450) is a potent non-structural protein 3/4A (NS3/4A) protease inhibitor with EC50s of 1 and 0.21 nM against HCV 1a and 1b, respectively.
Description :
Paritaprevir (ABT-450, Veruprevir) is a potent HCV NS3/4A protease inhibitor with EC50 of 1 and 0.21 nM for HCV GT 1a and 1b, respectively; demonstrates in vitro antiviral activity against HCV GT1-4 and GT6 (EC50=0.09 to 19 nM), and an EC50 of 0.09 nM against GT4a; The combination of paritaprevir, ritonavir, ombitasvir (an NS5A protein inhibitor), and dasabuvir (an NS5B non-nucleoside polymerase inhibitor) with or without RBV has been approved to treat HCV genotype 1 infections.
HCV Infection
Paritaprevir inhibits p-glycoprotein (p-gp) in vitro[1]. ABT-450 is an efficacious inhibitor of HCV NS3/4A protease, with 50% effective concentration values of 1.0, 0.21, 5.3, 19, 0.09, and 0.69 nM against stable HCV replicons with NS3 protease from genotypes 1a, 1b, 2a, 3a, 4a, and 6a, respectively. The CC50 of ABT-450 is more than 37 μM, resulting in an in vitro selectivity index of ≥37,000-fold. ABT-450 demonstrates activity across multiple HCV genotypes, with an EC50 of 5.3 nM against the genotype 2a JFH-1 subgenomic replicon[2]. Paritaprevir demonstrates in vitro antiviral activity against HCV GT1-4 and GT6 (EC50 range, 0.09 to 19 nM), with an EC50 of 0.09 nM against GT4a[3].
After oral administration, paritaprevir reaches maximum concentrations in a mean of 4-5 h with increases in exposure more than dose proportional. Absolute bioavailability is about 50% after administering with food. It displays high (about 97-99.9 %) plasma protein binding and has apparent volumes of distribution of 16.7L. Paritaprevir metabolism occurs via CYP3A4 (predominantly) and CYP3A5[1]. The combination of paritaprevir, ritonavir, ombitasvir (an NS5A protein inhibitor), and dasabuvir (an NS5B non-nucleoside polymerase inhibitor) with or without RBV has been approved to treat HCV genotype 1 infections1[2].