Ledipasvir (D-tartrate)

Ledipasvir D-tartrate is an inhibitor of the hepatitis C virus NS5A, with EC₅₀ values of 34 pM against GT1a and 4 pM against GT1b replicon. IC50 & Target: EC50: 34 pM (GT1a), 4 pM (GT1b)^[1] In Vitro: Ledipasvir has GT1a and 1b EC₅₀ values of 31 and 4 pM, respectively, and protein-adjusted EC₅₀ values of 210 pM (GT1a) and 27 pM (GT1b) and the intrinsic EC₅₀ of 39 is 310 fM for GT1a and 40 fM for GT1b. Ledipasvir is highly protein-bound both in human serum and in the cell-culture medium (containing 10% BSA) of the replicon assay^[1]. Ledipasvir exhibits an EC₅₀ value of 141 nM against the JFH/3a-NS5A replicon^[2]. In Vivo: Ledipasvir is remarkable not only on the basis of its high replicon potency but also on the basis of its low clearance, good bioavailability, and long half-lives in rat, dog, and monkey and low predicted clearance in human. The pharmacokinetics of Ledipasvir is measured in rats and dogs. Ledipasvir shows good half-lives (rat 1.83 ± 0.22 hr, dog 2.63 ± 0.18 hr) in plasma, low systemic clearance (CL), and moderate volumes of distribution (Vss) that are greater than total body water volume^[1].