title: Measuring ribavirin concentrations during the earliest stages of antiviral therapy for hepatitis C: potential relevance for treatment outcome.
abstract: BACKGROUND
  Correlations between ribavirin (RBV) concentrations and sustained virological response (SVR) to hepatitis C virus treatment have been demonstrated previously. As steady state is reached after several weeks of RBV treatment, dose modifications based on steady-state levels can only be applied relatively late in treatment, possibly too late to influence SVR rates. The authors aimed to determine whether measurement of early concentrations is useful to predict optimal steady-state RBV concentrations.
  
  
  METHODS
  In 61 treatment-naive genotype 1/4 patients RBV concentrations were determined in samples collected after 1, 2, 4, 8, 12, and 24 weeks of therapy. RBV concentrations were compared between responders and nonresponders; Receiver Operating Characteristic analyses were conducted to find optimal cut-off values to predict week 8 concentrations from earlier measurements.
  
  
  RESULTS
  Median week 8 RBV concentrations were significantly higher in patients with SVR compared with those without: 3.4 (interquartile range 2.4-3.9) versus 2.6 (interquartile range 2.0-3.5) mg/L (P < 0.05). RBV concentration at week 8 was an independent predictor of SVR [adjusted odds ratio 2.3 (95% confidence interval: 1.1-4.9; P = 0.03)]. The optimal cut-off value of week 8 RBV concentration to predict SVR was 2.20 mg/L [sensitivity 87%, specificity 40%, positive predictive value 64%, negative predictive value 71%]. Optimal cut-off values at weeks 1, 2, or 4 to predict an RBV concentration ≥2.20 mg/L at week 8 were 0.92, 1.29, and 1.67 mg/L, respectively, with positive predictive values and negative predictive values ranging from 88% to 91% and 71% to 86%, respectively.
  
  
  CONCLUSIONS
  RBV concentrations in the earliest stages of antiviral therapy predict therapeutic steady-state concentrations, allowing timely dose adjustments with potential implications for treatment outcome.
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht.
authors.forename: Lotte G
authors.initials: LG
authors.lastname: van Vlerken
authors.forename: Clara T M M
authors.initials: CT
authors.lastname: de Kanter
authors.forename: Greet J
authors.initials: GJ
authors.lastname: Boland
authors.forename: Anton M
authors.initials: AM
authors.lastname: van Loon
authors.forename: Hanneke
authors.initials: H
authors.lastname: van Soest
authors.forename: Ger H
authors.initials: GH
authors.lastname: Koek
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
authors.forename: Peter D
authors.initials: PD
authors.lastname: Siersema
authors.forename: Karel J
authors.initials: KJ
authors.lastname: van Erpecum
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000097:blood* / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D012254:Ribavirin / Q000097:blood* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin