title: Pharmacokinetics, safety and efficacy of a full dose sofosbuvir-based regimen given daily in hemodialysis patients with chronic hepatitis C.
abstract: Hepatitis C virus (HCV) infection is an independent risk factor for chronic kidney disease and leads to faster liver disease progression in patients requiring hemodialysis than in those with normal renal function. Little is known about the use of a sofosbuvir-containing regimen for infected patients on hemodialysis. We aimed to describe the pharmacokinetics, safety and efficacy of sofosbuvir in 2 dosing regimens and associated antiviral agents in HCV-infected patients requiring hemodialysis.
  
  
  
  Multicenter, prospective and observational study of patients receiving sofosbuvir, 400mg once daily (n=7) or 3 times a week (n=5), after hemodialysis with simeprevir, daclatasvir, ledipasvir or ribavirin was conducted. Drug plasma concentrations were determined by liquid chromatography-tandem mass spectrometry before and after a 4h hemodialysis and 1.5h after last drug intake at the end of hemodialysis.
  
  
  
  Plasma concentrations of sofosbuvir or its inactive metabolite sofosbuvir-007 did not accumulate with either regimen between hemodialysis sessions or throughout the treatment course. Sofosbuvir-007 extraction ratio (52%) was consistent with historical data. In one patient receiving the once daily regimen, sofosbuvir-007 half-life was slightly higher (38h) than for patients with normal renal function receiving a full dose. Hemodialysis did not remove any other associated anti-HCV agents. Clinical and biological tolerance was good for all patients. Two relapses occurred with the 3 times a week regimen and none with the once daily.
  
  
  
  A regimen including sofosbuvir, 400mg once daily, could be proposed for HCV-infected patients requiring hemodialysis and should be associated with close clinical, biological, cardiovascular, and therapeutic drug monitoring.
  
  
  
  Hepatitis C Virus (HCV) infection in hemodialysis patients is prevalent and aggressive. Effective anti-HCV treatment in these patients may stabilize their renal disease. However, sofosbuvir, the cornerstone of most anti-HCV-containing regimens, should not be administered to these patients until more data is available. In this pharmacokinetic study, sofosbuvir full dose (400mg once daily) administered every day with another direct antiviral agent did not accumulate in hemodialysis patients and was safe and effective.
authors.affiliation: Pharmaco-Toxicology Department, Bichat-Claude Bernard Hospital, APHP, Paris, France. Electronic address: audedesnoyer@gmail.com.
authors.forename: Aude
authors.initials: A
authors.lastname: Desnoyer
authors.affiliation: Gastroenterology Department, Bichat-Claude Bernard Hospital, APHP, Paris, France.
authors.forename: Dan
authors.initials: D
authors.lastname: Pospai
authors.affiliation: Pharmaco-Toxicology Department, Bichat-Claude Bernard Hospital, APHP, Paris, France.
authors.forename: Minh Patrick
authors.initials: MP
authors.lastname: Lê
authors.affiliation: Infectious Diseases & Tropical Department, Bichat-Claude Bernard Hospital, APHP, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Gervais
authors.affiliation: Gastroenterology Department, Robert Debré Hospital, Reims, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Heurgué-Berlot
authors.affiliation: Nephrology Department, ECHO-CMCM, Le Mans, France.
authors.forename: Achour
authors.initials: A
authors.lastname: Laradi
authors.affiliation: Infectious Diseases & Tropical Department, Bichat-Claude Bernard Hospital, APHP, Paris, France.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Harent
authors.affiliation: Infectious Diseases & Tropical Department, Bichat-Claude Bernard Hospital, APHP, Paris, France.
authors.forename: Adriana
authors.initials: A
authors.lastname: Pinto
authors.affiliation: Internal Medicine Department, Cochin Hospital, APHP, Paris Descartes University, Sorbonne Paris Cité, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Salmon
authors.affiliation: Gastroenterology Department, Foch Hospital, Suresnes, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Hillaire
authors.affiliation: Gastroenterology Department, Cochin Hospital, APHP, Paris Descartes University, Sorbonne Paris Cité, Inserm U1016, Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Fontaine
authors.affiliation: Infectious Diseases Department, Foch Hospital, Suresnes, France.
authors.forename: David
authors.initials: D
authors.lastname: Zucman
authors.affiliation: Internal Medicine Department, Louis-Mourier Hospital, APHP, Colombes, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Simonpoli
authors.affiliation: Clinical Pharmaco-Toxicology Department, University Hospital of Besançon, INSERM U1098, Besançon, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Muret
authors.affiliation: Virology Department, Bichat-Claude Bernard Hospital, APHP, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, IAME, INSERM UMR 1137, Paris, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Larrouy
authors.affiliation: Gastroenterology Department, Robert Debré Hospital, Reims, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bernard Chabert
authors.affiliation: Virology Department, Bichat-Claude Bernard Hospital, APHP, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, IAME, INSERM UMR 1137, Paris, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Descamps
authors.affiliation: Infectious Diseases & Tropical Department, Bichat-Claude Bernard Hospital, APHP, Paris, France.
authors.forename: Yazdan
authors.initials: Y
authors.lastname: Yazdanpanah
authors.affiliation: Pharmaco-Toxicology Department, Bichat-Claude Bernard Hospital, APHP, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, IAME, INSERM UMR 1137, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
mesh_terms: D000998:Antiviral Agents; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus; D019698:Hepatitis C, Chronic; D006801:Humans; D011446:Prospective Studies; D006435:Renal Dialysis; D012254:Ribavirin; D000069616:Simeprevir; D000069474:Sofosbuvir
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin; D000069616:Simeprevir; D000069474:Sofosbuvir
keywords: Hemodialysis; Hepatitis C Virus; Pharmacokinetics; Sofosbuvir