Pharmacodynamic and pharmacokinetic evaluation of the combination of daclatasvir/sofosbuvir/ribavirin in the treatment of chronic hepatitis C

Expert Opin Drug Metab Toxicol. 2018 Sep;14(9):901-910. doi: 10.1080/17425255.2018.1506765. Epub 2018 Aug 2.

Abstract

The combination of daclatasvir (DCV), sofosbuvir (SOF), and ribavirin (RBV) is a direct-acting antiviral (DAA) regimen for the treatment of hepatitis C virus (HCV) infection. The inclusion of newer effective DAAs such as SOF and DCV with high efficacy and excellent tolerance introduced a new scenario in HCV infection therapy: high rates of sustained virological response (SVR), shorter therapies, less toxicity, and interferon-free treatments. This combination was approved for the treatment of HCV in treatment-naive or treatment-experienced patients with chronic HCV genotype 1 or 3 infection. Areas covered: This review summarizes the pharmacokinetics, pharmacodynamics, efficacy, and safety of DCV plus SOF and RBV therapy in the treatment of HCV infection. The topics include data regarding drug absorption, distribution, metabolism, excretion, and antiviral activity strategies, such as clinical dose selection and treatment duration. Expert opinion: This combination, taken orally with or without food, has an excellent pharmacokinetic and pharmacodynamic profile. DAC/SOF/RBV achieves very high rates of SVR in treatment-naive and treatment-experienced patients with chronic HCV infection, including difficult-to-treat patients such as those with compensated cirrhosis, post-transplant recurrence, or HIV-1 co-infection.

Keywords: Daclatasvir; hepatitis C; pharmacodynamics; pharmacokinetics; ribavirin; sofosbuvir.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / pharmacology
  • Carbamates
  • Drug Combinations
  • Genotype
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / pharmacokinetics
  • Imidazoles / pharmacology
  • Pyrrolidines
  • Ribavirin / administration & dosage
  • Ribavirin / pharmacokinetics
  • Ribavirin / pharmacology
  • Sofosbuvir / administration & dosage
  • Sofosbuvir / pharmacokinetics
  • Sofosbuvir / pharmacology
  • Valine / analogs & derivatives

Substances

  • Antiviral Agents
  • Carbamates
  • Drug Combinations
  • Imidazoles
  • Pyrrolidines
  • Ribavirin
  • Valine
  • daclatasvir
  • Sofosbuvir