Peginterferon pharmacokinetics in African American and Caucasian American patients with hepatitis C virus genotype 1 infection.
OBJECTIVE
The relationship between serum peginterferon pharmacokinetics and pharmacodynamics and the early virologic response (EVR) to peginterferon and ribavirin therapy was assessed in patients with chronic hepatitis C virus (HCV) genotype 1 infection.


METHODS
A total of 333 patients (160 African Americans [AA] and 173 Caucasian Americans [CA]) who received peginterferon alpha-2a (180 microg/wk) without a dose modification during the initial 4 weeks of therapy were analyzed. Peginterferon and 2,5-oligoadenylate synthetase (2,5-OAS) serum levels were measured on days 0, 1, 2, 3, 7, 14, 28, 56, 84, and 168 of treatment. The EVR (>or=2-log(10) decline in HCV RNA levels by week 12 of therapy) was the primary virologic end point.


RESULTS
Peginterferon pharmacokinetics after the first dose were similar in AA and CA, but AA had greater peginterferon concentrations at days 1, 3, 14, and 28 (P < .05). AA had higher absolute serum 2,5-OAS levels on days 0, 1, 2, 3, 7, 14, 28, and 56 (P < .05), but the magnitude of 2,5-OAS induction during treatment were similar. AA patients showed a smaller decline in serum HCV RNA during the first 28 days of treatment (P < .001) and a lower EVR (65% vs 83%). AA and CA with EVR had significantly higher serum peginterferon concentrations and serum 2,5-OAS induction during the first 12 weeks than patients without an EVR.


CONCLUSIONS
Peginterferon alpha-2a pharmacokinetic and pharmacodynamic variability is associated with EVR in both AA and CA with HCV infection, but do not explain the racial disparity in combination treatment efficacy.
Howell
Charles D
CD
University of Maryland Baltimore School of Medicine, Baltimore, Maryland 21201, USA. chowell@umaryland.edu
Dowling
Thomas C
TC
Paul
Marika
M
Wahed
Abdus S
AS
Terrault
Norah A
NA
Taylor
Milton
M
Jeffers
Lennox
L
Hoofnagle
Jay H
JH
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data*; D000368:Aged; D019540:Area Under Curve; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology*; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012367:RNA, Viral / Q000187:drug effects; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000493:pharmacokinetics; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D019562:Viral Load; D044465:White People / Q000706:statistics & numerical data*
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a