Ledipasvir/sofosbuvir (Harvoni®), a fixed-dose combination tablet of an NS5A 
inhibitor ledipasvir and an NS5B polymerase inhibitor sofosbuvir, is approved in 
the US, European Union, Canada, and other regions for the treatment of chronic 
hepatitis C virus infection in adults. Following absorption, ledipasvir reaches 
maximum plasma concentrations (T max) 4-4.5 h post-dose and is eliminated with a 
terminal half-life (t 1/2) of 47 h. Sofosbuvir undergoes intracellular 
activation to an active triphosphate GS-461203 (not detected in plasma) and 
ultimately to GS-331007, a predominant circulating metabolite, which is the 
primary analyte of interest in clinical pharmacology studies. Sofosbuvir is 
rapidly absorbed and eliminated from plasma (T max: 0.8-1 h; t 1/2: 0.5 h). The 
peak plasma concentrations for GS-331007 are achieved between 3.5 and 4 h 
post-dose; the elimination t 1/2 for GS-331007 is 27 h. Ledipasvir/sofosbuvir 
exhibits a favorable clinical pharmacology profile; it can be administered once 
daily without regard to food and does not require dose modification in hepatitis 
C virus-infected patients with any degree of hepatic impairment or mild to 
moderate renal impairment. The pharmacokinetic profiles of ledipasvir, 
sofosbuvir, and GS-331007 (predominant circulating metabolite of sofosbuvir) are 
not significantly affected by demographic variables; 
pharmacokinetic/pharmacodynamic analyses reveal no exposure-response 
relationships for efficacy or safety. The review summarizes the clinical 
pharmacokinetics, pharmacodynamics, and pharmacokinetic/pharmacodynamic analyses 
for ledipasvir/sofosbuvir.