1.Clinical Pharmacokinetics of Dasabuvir    Clinical Pharmacokinetics    2017
Abstract：Dasabuvir is a nonstructural (NS) 5B non-nucleoside inhibitor of the hepatitis C virus (HCV) used in combination with ombitasvir/paritaprevir/ritonavir for the treatment of chronic HCV infection. It is primarily metabolized by cytochrome P450 (CYP) 2C8, with a minor contribution from CYP3A. Biotransformation of dasabuvir forms the M1 metabolite, which retains antiviral activity. Dasabuvir exhibits linear pharmacokinetics with a terminal half-life of approximately 5–8 h, allowing for twice-daily dosing. The M1 metabolite of dasabuvir is the major metabolite in plasma and has a half-life similar to that of dasabuvir. Dasabuvir exposures in Asian subjects are comparable with Caucasian subjects. The pharmacokinetic characteristics of dasabuvir are similar between healthy subjects and HCV-infected patients, and are not appreciably altered by mild , moderate, or severe renal impairment or dialysis. Dasabuvir pharmacokinetic parameters were not significantly altered in subjects with mild or mo derate hepatic impairment; however, exposures were significantly increased in subjects with severe hepatic impairment. Dasabuvir should be administered with food to maximize absorption. Coadministration of dasabuvir with a strong CYP2C8 inhibitor increased dasabuvir exposures by greater than tenfold, whereas coadministration with strong CYP3A inhibitors increased dasabuvir exposures by less than 50%. Furthermore, coadministration of dasabuvir with a CYP3A inducer decreased dasabuvir exposures by 55–70%. Coadministration of dasabuvir with strong CYP2C8 inhibitors or strong CYP3A/CYP2C8 inducers is contraindicated. Results from drug several interaction studies demonstrated that dasabuvir in combination with ombitasvir/paritaprevir/ritonavir can be coadministered with most comedications that are commonly prescribed in HCV-infected patients.
2.  Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir: A Review in Chronic HCV Genotype 1 Infection    Drugs    2015
Abstract：A fixed-dose tablet comprising ombitasvir (an NS5A replication complex inhibitor), paritaprevir (an NS3/4A protease inhibitor) and ritonavir (a cytochrome P450 inhibitor) taken in combination with dasabuvir (an NS5B polymerase inhibitor) is indicated for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection in several countries, including the USA (copackaged as Viekira Pak™) and those of the EU (Viekirax® and Exviera®). In phase II and III trials, this interferon-free regimen, taken ± ribavirin, provided high rates of sustained virological response 12 weeks post-treatment in adults with chronic HCV genotype 1a or 1b infection, including those with compensated cirrhosis, liver transplants or HIV-1 co-infection. The regimen was generally well tolerated, with nausea, insomnia, asthenia, pruritus, other skin reactions and fatigue being among the most common tolerability issues., ombitasvir/ Thusparitaprevir/ritonavir plus dasabuvir is an effective interferon-free, direct-ac ting antiviral regimen for use ± ribavirin in a broad range of adults chronically infected with HCV genotype 1.