Ledipasvir D-tartrate (GS-5885 D-tartrate) is an HCV NS5A inhibitor that suppresses viral overphosphorylation and replication, and is used for the treatment of hepatitis C virus.

GT1b:4 pM, GT1a:34 pM (EC50)

Method:
Ledipasvir D-tartrate antiviral activity against HCV genotypes 1a and 1b and protein-adjusted EC50 values were determined using replicon systems. Protein binding and inhibitory effects on the JFH/3a-NS5A replicon were also evaluated.

Result:
Ledipasvir D-tartrate exhibited EC50 values of 31 pM and 4 pM against genotypes 1a and 1b, respectively, with protein-adjusted EC50 values of 210 pM and 27 pM. It showed high protein binding. The EC50 against the JFH/3a-NS5A replicon was 141 nM. [2]

Method:
Pharmacokinetic parameters of Ledipasvir D-tartrate, including plasma half-life, systemic clearance (CL), and steady-state volume of distribution (Vss), were measured in rats and dogs to evaluate its in vivo pharmacokinetic properties.

Result:
Ledipasvir D-tartrate exhibited favorable plasma half-lives in rats (1.83 ± 0.22 hours) and dogs (2.63 ± 0.18 hours), low systemic clearance, and moderate Vss values greater than total body water volume. The drug demonstrated good bioavailability and long half-lives in various primates, with predicted low clearance in humans. [1]