Daclatasvir (DCV) is a potent hepatitis C virus (HCV) NS5A replication complex inhibitor with pangenotypic (1-6) activity in vitro. Daclatasvir inhibits the HCV nonstructural protein NS5A.Recent research suggests that it targets two steps of the viral replication process, enabling rapid decline of HCV RNA.Twelve or 16 weeks of treatment with daclatasvir, in combination with peginterferon alfa-2a and ribavirin, is well tolerated and effective therapy for patients with HCV genotype 2 or 3 infections. Daclatasvir-containing regimens could reduce the duration of therapy for these patients. Daclatasvir plus asunaprevir provided high sustained virological response rates in treatment-naive, non-responder, and ineligible, intolerant, or ineligible and intolerant patients, and was well tolerated in patients with HCV genotype 1b infection.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 148 mg/mL|
Evaluation of drug-drug interaction between daclatasvir and methadone or buprenorphine/naloxone.
Garimella T, et al. J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19628. PMID: 25394132.
Asymmetric Binding to NS5A by Daclatasvir (BMS-790052) and Analogs Suggests Two Novel Modes of HCV Inhibition.
Nettles JH, et al. J Med Chem. 2014 Nov 3. PMID: 25365735.
Daclatasvir plus Peginterferon and Ribavirin is Non-inferior to Peginterferon and Ribavirin Alone, and Reduces Duration of Treatment for HCV Genotype 2 or 3 Infection.
Dore GJ, et al. Gastroenterology. 2014 Oct 10;S0016-5085(14)01206-2.. PMID: 25311593.
All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study.
Manns M, et al. Lancet. 2014 Jul 26;S0140-6736(14)61059-X. PMID: 25078304.
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Paritaprevir (ABT-450) is a potent non-structural protein 3/4A (NS3/4A) protease inhibitor with EC50 values of 1 and 0.21 nM for HCV 1a and 1b, respectively.
Velpatasvir is a second-generation NS5A inhibitor that inhibits hepatitis C viral replication through acting on the crucial "membranous web" that facilitates RNA replication.
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