title: The ARRIBA concept: adequate resorption of ribavirin.
abstract: BACKGROUND
  Adequate ribavirin exposure is essential for optimal sustained virological response (SVR) rates in chronic HCV treatment. It has been proposed that the area under the concentration-time curve up to 4 h after intake of ribavirin (AUC0-4 h) of the first weight-based ribavirin dose should be ≥1.755 mg•h/l to guarantee the highest chance of SVR. Our ARRIBA concept comprises a test dose of ribavirin to select the optimal starting dose to achieve adequate exposure. This study aims to evaluate whether adequate exposure can be achieved after dose advice based on the AUC0-4 h of a single weight-based ribavirin test dose.
  
  
  METHODS
  (Formerly) HCV-infected subjects received a single weight-based ribavirin test dose (<75 kg: 400 mg; ≥75 kg: 600 mg) and the AUC0-4 h was calculated. If ribavirin AUC0-4 h was ≥1.755 mg•h/l, subjects received the same dose 4 weeks later; if the AUC0-4 h was <1.755 mg•h/l, an adjusted dose was administered. The ribavirin AUC0-4 h was recorded again. The primary outcome was the proportion of subjects with an AUC0-4 h ≥1.755 mg•h/l after the second dose.
  
  
  RESULTS
  A total of 26 subjects were included. The geometric mean (95% CI) ribavirin AUC0-4 h was 1.67 (1.44-1.92) mg•h/l with 9 subjects (35%) reaching the target AUC on day 1. Thus, on day 29, 17 subjects (65%) received an adjusted dose. The geometric mean (95% CI) AUC0-4 h increased to 1.90 (1.62-2.21) mg•h/l and then 16 subjects (62%) had an AUC0-4 h ≥1.755 mg•h/l, which is significantly higher than day 1 (P<0.05).
  
  
  CONCLUSIONS
  Our ARRIBA concept of a ribavirin test dose, with dose adjustment if necessary, leads to an increased proportion of patients with an AUC≥1.755 mg•h/l compared to traditional weight-based ribavirin dosing.
authors.affiliation: Pharmacy, Radboud University Medical Center, Nijmegen, the Netherlands. klaartje.dekanter@radboudumc.nl.
authors.forename: Clara T M M
authors.initials: CT
authors.lastname: de Kanter
authors.forename: Ludi
authors.initials: L
authors.lastname: Koning
authors.forename: Floor A C
authors.initials: FA
authors.lastname: Berden
authors.forename: Jan-Christian
authors.initials: JC
authors.lastname: Wasmuth
authors.forename: Karin J T
authors.initials: KJ
authors.lastname: Grintjes-Huisman
authors.forename: Brigitta
authors.initials: B
authors.lastname: Becker
authors.forename: Angela P H
authors.initials: AP
authors.lastname: Colbers
authors.forename: Monique M B
authors.initials: MM
authors.lastname: Roukens
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Rockstroh
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
authors.forename: Robert J
authors.initials: RJ
authors.lastname: de Knegt
authors.forename: Anton S M
authors.initials: AS
authors.lastname: Dofferhoff
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D060085:Coinfection; D004305:Dose-Response Relationship, Drug; D005260:Female; D015658:HIV Infections / Q000150:complications; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012254:Ribavirin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin