title: The pharmacokinetics of peginterferon alfa-2a and ribavirin in African American, Hispanic and Caucasian patients with chronic hepatitis C.
abstract: BACKGROUND
  Amongst Caucasian, Hispanic and African Americans with genotype 1 hepatitis C virus (HCV), there is a wide variation in response to treatment with peginterferon alfa-2a (PEG-IFN alfa-2a) and ribavirin.
  
  
  OBJECTIVE
  To evaluate the pharmacokinetics (PK) of PEG-IFN alfa-2a and ribavirin among these three groups.
  
  
  METHODS
  Forty-seven patients with genotype 1 CHC (17 African Americans, 14 Hispanics and 16 Caucasians) received 8 weeks of PEG-IFN alfa-2a (180 μg/week) and ribavirin (1000 or 1200 mg/day). PEG-IFN alfa-2a serum concentrations and ribavirin plasma concentrations were measured following the first dose and at week 8. Pharmacokinetic parameters (C(max), T(max), AUC, CL/F) were estimated using noncompartmental methods.
  
  
  RESULTS
  There was no difference in the pharmacokinetic parameters for PEG-IFN alfa-2a following single-dose or steady-state administration between African American or Hispanic patients compared with Caucasian patients. Ribavirin pharmacokinetic parameters were similar between Hispanic and Caucasian patients for single-dose and steady-state administration. The single-dose C(max) was 33% lower (P < 0.05) in African American compared with Caucasian patients. Other ribavirin single-dose and steady-state pharmacokinetic parameters were slightly decreased (approximately 20% lower) in African American patients, but were not considered clinically meaningful.
  
  
  CONCLUSIONS
  No differences were observed in PEG-IFN alfa-2a pharmacokinetic parameters between African American or Hispanic patients compared with Caucasian patients. For ribavirin, no differences were observed in pharmacokinetic parameters between Hispanic and Caucasian patients. While a trend towards increased ribavirin clearance and decreased exposure was observed in African American patients vs. Caucasian patients, the differences were small and not considered clinically meaningful (Clinical Trial Number: NP17354).
authors.affiliation: Roche, Nutley, NJ, USA. barbara.brennan@roche.com
authors.forename: B J
authors.initials: BJ
authors.lastname: Brennan
authors.forename: P N
authors.initials: PN
authors.lastname: Morcos
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.forename: S D
authors.initials: SD
authors.lastname: Blotner
authors.forename: R
authors.initials: R
authors.lastname: Morrison
authors.forename: C H
authors.initials: CH
authors.lastname: Hagedorn
authors.forename: T C
authors.initials: TC
authors.lastname: Marbury
authors.forename: M
authors.initials: M
authors.lastname: Sulkowski
authors.forename: J F
authors.initials: JF
authors.lastname: Grippo
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D012254:Ribavirin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D044465:White People / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a