Effect of Hemodialysis on Efficacy and Pharmacokinetics of Sofosbuvir Coformulated with Either Daclatasvir or Ledipasvir in Patients with End-Stage Renal Disease

Blood Purif. 2020;49(6):692-699. doi: 10.1159/000499161. Epub 2020 Apr 14.

Abstract

Background/aims: Direct-acting antivirals (DAAs) play a key role in the eradication of hepatitis C virus (HCV) infection. However, limited data are available on DAA for treating HCV infection in hemodialysis (HD) patients. This study was to evaluate the pharmacokinetic characteristics and effectiveness of daclatasvir/sofosbuvir (DAC/SOF) and ledipasvir/SOF (LDV/SOF) in HD patients.

Methods: Seven patients were given SOF coadministered with DAC or LDV once daily for 12 weeks. The plasma concentrations of SOF007, DAC, and LDV were determined by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.

Results: A sustained virologic response in week 12 (SVR12) was achieved in 6 (100%) patients, except for 1 patient dying due to severe cerebral hemorrhage not related to antiviral therapy. The extraction ratio of SOF007 was 66.67%, and the estimated HD clearance of SOF007 was 5.65 L/h.

Conclusion: The combination of SOF with either DAC or LDV is well tolerated and offers high SVR12 in HD patients.

Keywords: Direct-acting antivirals; Hemodialysis; Hepatitis C; Pharmacokinetic; Removal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Benzimidazoles / pharmacokinetics*
  • Benzimidazoles / therapeutic use
  • Carbamates / pharmacokinetics*
  • Carbamates / therapeutic use
  • Clinical Trials as Topic
  • Drug Monitoring
  • Drug Therapy, Combination
  • Female
  • Fluorenes / pharmacokinetics*
  • Fluorenes / therapeutic use
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / drug therapy
  • Humans
  • Imidazoles / pharmacokinetics*
  • Imidazoles / therapeutic use
  • Kidney Failure, Chronic / complications*
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Pyrrolidines / pharmacokinetics*
  • Pyrrolidines / therapeutic use
  • Renal Dialysis* / adverse effects
  • Renal Dialysis* / methods
  • Sofosbuvir / pharmacokinetics*
  • Sofosbuvir / therapeutic use
  • Treatment Outcome
  • Valine / analogs & derivatives*
  • Valine / pharmacokinetics
  • Valine / therapeutic use

Substances

  • Benzimidazoles
  • Carbamates
  • Fluorenes
  • Imidazoles
  • Pyrrolidines
  • ledipasvir
  • Valine
  • daclatasvir
  • Sofosbuvir