Pharmacokinetics and pharmacodynamics of sofosbuvir and ledipasvir for the treatment of hepatitis C

Abstract

The sofosbuvir (SOF) plus ledipasvir (LDV) fixed dose combination is the first direct action antiviral (DAA) single-treatment regimen (STR) to be commercialized. It is approved for the treatment of Hepatitis C virus (HCV) genotypes 1,3,4,5 and 6. Following approval in 2014, new pharmacokinetics and pharmacodynamics data were reported, which led to important clinical applications. Areas covered: This article reviews the pharmacokinetic and pharmacodynamic properties of the SOF/LDV fixed dose combination for the treatment of HCV. The topics covered include data regarding the drug´s absorption, distribution, metabolism and excretion and antiviral activity strategies such as the clinical dose selection and treatment duration. Expert opinion: The SOF/LDV fixed dose combination has good pharmacological properties that lead to a high sustained virological response after 12 or 24 weeks of treatment; there is minimal interference with other drugs or associated renal or hepatic impairment, such that dose adjustment is not necessary.

Systematic review with meta‐analysis: neuroimaging in hepatitis C chronic infection

“…Furthermore, the evidence of viral quasi‐species diversity between the central nervous system and liver, supports the notion of independent viral evolution, rendering the central nervous system a potential source of relapse after anti‐viral therapy . Considering the questionable blood‐brain barrier penetration ability of the new direct acting anti‐virals (DAAs), such reservoir should be taken into account in long‐term rebound or outcomes. Late viral relapses are extremely rare after successful treatment with DAAs .…”

“…Publication bias of this group of articles was examined in a funnel plot of MD against its standard error, and the Begg's test was used to test funnel plot's asymmetry. Nevertheless, such analysis was not possible because of the poor number of studies included in the meta‐analyses (less than 10) . Statistical analyses were performed using SPSS (version 20.0 for Windows; SPSS, Inc, Chicago, IL, USA) and Review Manager (RevMan, Version 5.3, Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014).…”

Efficacy of sofosbuvir and ledipasvir in an HCV+ gastro-resected patient

“…1 The arrival of the second-generation direct-acting antivirals (DAAs), due to their optimal efficacy and tolerability, represented the first major turning point for the potential eradication of HCV infection. 3,4 LDV median peak concentrations following SOF/LDV administration occur 4-hour post-dose. 2 The pharmacokinetics of SOF/LDV has been described, but bioavailability of the drugs is not completely understood in humans.…”

“…2 The pharmacokinetics of SOF/LDV has been described, but bioavailability of the drugs is not completely understood in humans. 3,4 LDV median peak concentrations following SOF/LDV administration occur 4-hour post-dose. SOF is absorbed quickly and metabolized into the pharmacologically active nucleoside analogue triphosphate GS-461203.…”

“…The major elimination pathways of LDV and SOF metabolites are biliary excretion and renal clearance, respectively. 5,6 The need for an acidic gastric environment for complete absorption of LDV has been demonstrated, 4 but the data remains controversial in real-life studies. 7,8 No data currently exists on the efficacy and safety of SOF/LDV in patients with partial or complete gastric resection.…”