RIBAVIRIN PHARMACOKINETICS, RACE AND OUTCOME OF HEPATITIS C TREATMENT

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chronic hepatitis C virus (HCV) is the most common cause for liver cirrhosis and a major etiology for primary hepatocellular carcinoma (HCC) in the United States. HCV is 2 times more prevalent in African Americans (AA) than in Caucasian Americans (CA), and appear to be an important cause for the higher incidence of HCC among AA. Pegylated interferon (PEGIFN) plus ribavirin treatments is the most effective treatment for chronic hepatitis C virus (HCV) infections. HCV is eradicated in 55% of treated patients. For unclear reasons, AA have a lower probability of clearing HCV than CA during treatment. There were no major differences in the pharmacokinetics of PEGIFN between AA and CA in Virahep-C study. Others have found a significant correlation between ribavirin serum concentrations and both virologic responses and ribavirin toxicity in patients receiving PEGIFN combination therapy. Concerning ribavirin pharmacokinetics, a pilot study found a significantly lower maximum ribavirin concentrations (Cmax) after the first-dose in AA compared to CA. There was trend toward lower ribavirin exposure measured by the area-under-the concentration by time curve (AUC) and higher apparent ribavirin clearance in AA. Thus, we hypothesize that ribavirin pharmacokinetics differ between AA and CA HCV genotype 1 patients and that this difference contributes to the lower efficacy of PEGIFN and ribavirin in AA. This project has two components: 1) a retrospective study to compare ribavirin pharmacokinetic (PK) (ribavirin plasma concentrations, area under the concentration time curve, and clearance) and HCV eradication in 75 AA and 75 CA who participated in the NIDDK VIRAHEP-C study (2001-2006); and 2) a prospective comparison of ribavirin pharamcokinetics after the first dose and at steady state (6 weeks) in 70 AA and 70 CA patients during pegylated interferon and ribavirin treatment for chronic HCV.