title: Ribavirin plasma concentration measurements in patients with hepatitis C: early ribavirin concentrations predict steady-state concentrations.
abstract: BACKGROUND
  Ribavirin is an essential component in the treatment of chronic hepatitis C (HCV) infection. Although ribavirin dose is weight-based, data in the literature suggest large between-patient variability in plasma ribavirin concentrations. Recent studies indicate that higher ribavirin exposure results in higher sustained viral response rates. Monitoring ribavirin concentration is suggested in the literature, but it is unclear at what time point during treatment plasma ribavirin concentrations should be monitored.
  
  
  OBJECTIVE
  To investigate the association between early plasma ribavirin concentrations and ribavirin dosing with steady-state (Css) concentration and the between- and within-patient variability in plasma ribavirin concentration in clinical practice.
  
  
  METHODS
  We performed a prospective observational cohort study in patients with HCV who received pegylated interferon in combination with oral weight-based ribavirin (12-15 mg/kg) twice daily. Trough plasma ribavirin concentrations at Weeks 1, 2, 4, 8, 12, 16, 20, and 24 were studied using a validated high-performance liquid chromatography assay.
  
  
  RESULTS
  In total, 53 patients (37 male, 16 female) with a mean age of 51 years (range, 26-68 years) were included and 209 samples were collected. There was a significant correlation between Week 2 as well as Week 4 and plasma ribavirin Css (r = 0.589 and r = 0.714, P < 0.05, respectively). Ribavirin Css was reached at Week 8 of HCV treatment. There was no correlation between dose in mg/kg and Css (r = 0.181, P = 0.263). The between- and within-patient coefficients of variation of plasma ribavirin concentrations at Week 8 and beyond were 43% and 13%, respectively.
  
  
  CONCLUSIONS
  In HCV-infected patients, ribavirin steady-state concentrations can be predicted by measurement of concentrations made early after the start of therapy.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. S.Slavenburg@MDL.umcn.nl
authors.forename: Serena
authors.initials: S
authors.lastname: Slavenburg
authors.forename: Hanneke W H A
authors.initials: HW
authors.lastname: Huntjens-Fleuren
authors.forename: Ton S M
authors.initials: TS
authors.lastname: Dofferhoff
authors.forename: Clemens
authors.initials: C
authors.lastname: Richter
authors.forename: Peter P
authors.initials: PP
authors.lastname: Koopmans
authors.forename: Corrien P W G M
authors.initials: CP
authors.lastname: Verwey-Van Wissen
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015331:Cohort Studies; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D006526:Hepatitis C / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin