title: Impact of ribavirin plasma level on sustained virological response in patients treated with pegylated interferon and ribavirin for chronic hepatitis C.
abstract: BACKGROUND
  The main goal of therapy in hepatitis C virus (HCV) infection is to achieve a sustained virological response (SVR). However, the impact of the pharmacological properties of ribavirin on the SVR has not been fully investigated.
  
  
  OBJECTIVE
  To evaluate, through a prospective study, the association between ribavirin plasma level and SVR response in HCV patients treated with pegylated interferon (PEG-IFN) and ribavirin.
  
  
  METHODS
  Patients treated with PEG-IFN and ribavirin had plasmatic ribavirin dosage at weeks 4 and 12. SVR was evaluated 6 months after the end of treatment.
  
  
  RESULTS
  At week 4, a strong correlation was found between HCV-RNA and C(min) of ribavirin plasma level (r = -0.376, P = 0.002) and AUC(0-->12h) of ribavirin plasma level (r = -0.277, P = 0.018). At week 12, a strong correlation was found between HCV-RNA and C(min) of ribavirin plasma level (r = -0.384, P < 0.0001) and AUC(0-->12h) of ribavirin plasma level (r = -0.257, P = 0.002). In genotype 1 patients, AUC(0-->12h) ribavirin and C(min) were significantly correlated with negative HCV-RNA at week 12 and SVR. In the multiple logistic regression model, the only factor independently associated with SVR in genotype 1 patients was negative HCV-RNA at week 12.
  
  
  CONCLUSIONS
  C(min) of ribavirin at weeks 4 and 12 was significantly higher in sustained virological responders compared with relapser or nonresponder patients. However, in genotype 1 patients, plasma ribavirin level at weeks 4 and 2 was not associated with SVR.
authors.affiliation: Laboratoire de Pharmacocinétique et de Pharmacie Clinique EA2968, Université Victor Segalen Bordeaux 2, Bordeaux, France.
authors.forename: D
authors.initials: D
authors.lastname: Breilh
authors.forename: J
authors.initials: J
authors.lastname: Foucher
authors.forename: L
authors.initials: L
authors.lastname: Castéra
authors.forename: P
authors.initials: P
authors.lastname: Trimoulet
authors.forename: S
authors.initials: S
authors.lastname: Djabarouti
authors.forename: W
authors.initials: W
authors.lastname: Merrouche
authors.forename: P
authors.initials: P
authors.lastname: Couzigou
authors.forename: M-C
authors.initials: MC
authors.lastname: Saux
authors.forename: V
authors.initials: V
authors.lastname: de Lédinghen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b