1. Pharmacokinetic and pharmacodynamic evaluation of daclatasvir, asunaprevir plus beclabuvir as a fixed-dose co-formulation for the treatment of hepatitis C.
- Author
-
Esposito I, Marciano S, and Trinks J
- Subjects
- Administration, Oral, Antiviral Agents pharmacokinetics, Antiviral Agents pharmacology, Benzazepines administration & dosage, Benzazepines pharmacokinetics, Benzazepines pharmacology, Carbamates, Drug Combinations, Genotype, Hepacivirus isolation & purification, Hepatitis C virology, Humans, Imidazoles administration & dosage, Imidazoles pharmacokinetics, Imidazoles pharmacology, Indoles administration & dosage, Indoles pharmacokinetics, Indoles pharmacology, Isoquinolines administration & dosage, Isoquinolines pharmacokinetics, Isoquinolines pharmacology, Japan, Pyrrolidines, Sulfonamides administration & dosage, Sulfonamides pharmacokinetics, Sulfonamides pharmacology, Valine analogs & derivatives, Antiviral Agents administration & dosage, Hepacivirus genetics, Hepatitis C drug therapy
- Abstract
Introduction: Many reports have evaluated the clinical efficacy and safety of the fixed-dose all-oral combination of daclatasvir, asunaprevir, and beclabuvir (DCV-TRIO), which was approved in Japan in December 2016 for the treatment of hepatitis C genotype (GT)-1 infection. Areas covered: This article reviews the pharmacodynamic and pharmacokinetic properties of the DCV-TRIO combination. The topics covered include data regarding the drug's absorption, distribution, metabolism, excretion, and antiviral activity strategies. Its therapeutic efficacy and safety in GT-1 infection from phase 2/3 clinical trials are also discussed. Expert opinion: The ideal regimen for the treatment of Hepatitis C virus infection should be potent, pangenotypic, Ribavirin-free, safe, co-formulated, and affordable. Considering these characteristics, DCV-TRIO is neither pangenotypic nor potent enough against GT-1a, regardless of the presence or absence of cirrhosis. Other potential limitations of this regimen are its dosification (twice-daily), and the fact that since it includes a protease inhibitor, it is contraindicated in decompensated cirrhosis. For these reasons, it has only been approved in Japan, where more than 70% of the patients are infected with GT-1b. However, this co-formulation might still have a place in the treatment of non-cirrhotic patients infected with GT-1b provided that massive access to treatment is facilitated.
- Published
- 2018
- Full Text
- View/download PDF