Influence of the dual combination of Statin(s) and Direct Acting Antiviral (DAA) Drug(s): Pharmacokinetic study

Abstract

Daclatasvir (DCV) is the first-in-class HCV NS5A inhibitor that has anti-viral effect across multiple HCV genotypes. Many Studies showed that DCV is a substrate of efflux transporters including P-gp. The major route of elimination of DCV is via CYP3A4-mediated metabolism and P-glycoprotein (P-gp) excretion and intestinal secretion. It was proved that the use of statins improved the Sustained virological response (SVR) rates to antiviral therapy, decreased progression of liver fibrosis and decreased incidence of HCC among HCV patients. Atorvastatin is both substrate and inhibitor of P-gp. P-gp can potentially decrease the absorption and oral bioavailability and reduce the retention time of many drugs including DAAs and thus the use of P-gp modulators is a source of DDIs. This has directed this research towards testing the pharmacokinetic interaction between atorvastatin and the direct acting antiviral drug daclatasvir, and the possible underlying