RIBAVIRIN PHARMACOKINETICS, RACE AND OUTCOME OF HEPATITIS C TREATMENT

利巴韦林丙型肝炎治疗的药代动力学、种族和结果

• 批准号: 7951172
• 负责人: CHARLES D HOWELL
• 金额: $ 3.15万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7951172
• 关键词: African American; American; Area; Chronic Hepatitis C; Clinical Research; Combined Modality Therapy; Computer Retrieval of Information on Scientific Projects Database; Dose; Drug Kinetics; Etiology; Funding; Genotype; Grant; Hepatitis C; Hepatitis C virus; Incidence; Institution; Interferons; Liver Cirrhosis; Measures; National Institute of Diabetes and Digestive and Kidney Diseases; Outcome; Patients; Pilot Projects; Plasma; Primary carcinoma of the liver cells; Probability; Race; Research; Research Personnel; Resources; Retrospective Studies; Ribavirin; Serum; Source; Time; Toxic effect; United States; United States National Institutes of Health; caucasian American; effective therapy; prospective; response; trend

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 慢性丙型肝炎病毒（HCV）是美国肝硬化的最常见原因，也是美国原发性肝细胞癌（HCC）的主要病因。在非洲裔美国人（AA）中，HCV比白人美国人（CA）高两倍，并且似乎是AA中HCC发病率更高的重要原因。 Pegymet干扰素（PEGIFN）加上利巴韦林治疗是慢性丙型肝炎病毒（HCV）感染的最有效治疗方法。在55％的治疗患者中消除了HCV。由于不清楚的原因，AA在治疗过程中比CA的清除HCV的概率低。在Virahep-C研究中，AA和CA之间的PEGIFN药代动力学没有主要差异。其他人发现，在接受PEGIFN联合疗法的患者中，利巴韦林血清浓度与病毒学反应与利巴韦林毒性之间存在显着相关性。关于利巴韦林药代动力学，一项试点研究发现，与Ca相比，AA的一剂量后，最大利巴韦林浓度（CMAX）明显降低。通过时间曲线（AUC）的浓度（AUC）和AA中明显的可利巴韦林清除率较低的面积浓度测量的利巴韦林暴露趋势。因此，我们假设AA和CA HCV基因型1患者之间的利巴韦林药代动力学有所不同，并且这种差异有助于Pegifn和Irabavirin在AA中的疗效降低。该项目有两个组成部分：1）一项回顾性研究，以比较利巴韦林药代动力学（PK）（Ribavirin血浆浓度，浓度时间曲线和间隙下的面积）和75 AA和75个CA的HCV消除，他们参加了NIDDK Virahep-C研究（2001-2006）； 2）在初次剂量后的利巴韦林磷酸脂蛋白药物的前瞻性比较（在70个AA和70名CA患者中，在慢性HCV中的70个AA和70名CA患者中进行稳态（6周）。