Ribavirin Pharmacokinetics, Race and HCV Treatment
利巴韦林药代动力学、种族和 HCV 治疗
基本信息
- 批准号:7440199
- 负责人:
- 金额:$ 18.19万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-06-15 至 2011-03-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAfrican AmericanAftercareAmericanAnemiaAreaCessation of lifeChronicChronic Hepatitis CCirrhosisClinical ResearchClinical TrialsCombined Modality TherapyDoseDrug KineticsEtiologyExhibitsFutureGenotypeHepatitis C virusHospital MortalityIncidenceInfectionInterferon-alphaInterferonsKineticsLeadLiver CirrhosisLiver diseasesMarylandMeasuresMorbidity - disease rateNumbersOutcomePatientsPegylated Interferon AlfaPharmaceutical PreparationsPilot ProjectsPlasmaPolymerasePopulationPrevalencePrimary carcinoma of the liver cellsProbabilityProspective StudiesProtease InhibitorRNA Polymerase InhibitorRaceRateRelapseRelative (related person)Relative RisksResistanceRibavirinRisk FactorsSerumTestingTimeToxic effectTreatment EfficacyUnited StatesUniversitiesViralVirusWeekbasecaucasian Americandayhealth disparityhepatitis C virus NS3 proteinimprovedmathematical modelmortalitynovelresponsetreatment durationtrendviral RNA
项目摘要
DESCRIPTION (provided by applicant): Chronic hepatitis C virus (HCV) is the most common cause for liver cirrhosis and a major risk factor for primary hepatocellular carcinoma (HCC) in the United States. In the absence of highly effective treatment, the number of patients with decompensated liver cirrhosis and primary HCC related to HCV is projected to increase by 200% and the number of deaths by 300% by the year 2030. HCV is 2 times more prevalent and is associated with worse outcome in African Americans (AA) than in Caucasian Americans (CA). Ironically, AA infected with HCV genotype 1 exhibit significantly lower rates of HCV clearance following treatment pegylated interferon alfa (PEGIFNa) in combination with ribavirin. More effective treatments for HCV genotype 1 infections in AA are needed to reduce the future health disparity between AA and CA with HCV. When combined with IFN ribavirin decreases HCV relapse rate following treatment resulting in a 2-3 higher sustained virological rate by compared to IFN alone. Several recent studies lead us to hypothesize that ribavirin pharmacokinetics is different in AA and CA HCV genotype 1 patients and that this difference contributes to the lower efficacy of PEGIFN and ribavirin in AA: 1) there is a significant correlation between both the ribavirin dose and ribavirin serum concentration during treatment and virologic response rates in patients receiving PEGIFN combination therapy; 2) a recent mathematical model HCV RNA kinetics suggests ribavirin treatment is more important to HCV clearance in patients in whom IFN therapy is less effective such as AA infected with HCV genotype 1; 3) a pilot study by Brennan et al. found increased ribavirin clearance and lower ribavirin serum levels in AA compared to CA HCV patients. The long-term objective of this project is to reduce the disparity in the efficacy of treatment for HCV between AA and CA. The project has 2 specific aims: 1) to determine the relationship between ribavirin plasma levels and virologic response and anemia in AA and CA HCV genotype 1 patients during PEGIFN alfa-2a and ribavirin treatment in the Virahep-C study; and 2) to determine ribavirin pharmacokinetics in AA and CA infected with HCV genotype 1. In all probability, PEGIFN and ribavirin or a ribavirin-like drug will remain a component of future HCV treatments that include HCV polymerase and protease inhibitors. The results of this study will clarify the importance of ribavirin pharmacokinetics during PEGIFN and ribavirin treatment, help to optimize ribavirin dose, and ultimately improve the efficacy of HCV genotype 1 treatment in AA as well as in CA patients. This proposed study seeks to improve the efficacy of current therapy for chronic hepatitis C (HCV) in African Americans infected with genotype 1 of the virus, the most resistant to treatment. More effective treatments are necessary to reduce the disparities between African Americans and Caucasian Americans in sickness and deaths related to HCV liver disease.
描述(由申请人提供):慢性丙型肝炎病毒(HCV)是美国肝硬化的最常见原因,也是原发性肝细胞癌(HCC)的主要危险因素。在缺乏高效治疗的情况下,到 2030 年,与 HCV 相关的失代偿性肝硬化和原发性 HCC 患者数量预计将增加 200%,死亡人数将增加 300%。HCV 的患病率是原来的 2 倍,并且非裔美国人 (AA) 的结果比白种人美国人 (CA) 的结果更差。讽刺的是,感染 HCV 基因型 1 的 AA 在接受聚乙二醇化干扰素 α (PEGIFNa) 与利巴韦林联合治疗后,HCV 清除率显着降低。需要对 AA 地区的 HCV 基因型 1 感染进行更有效的治疗,以缩小 AA 和 CA 之间未来因 HCV 造成的健康差距。当与 IFN 联合使用时,利巴韦林可降低治疗后 HCV 复发率,与单独使用 IFN 相比,持续病毒学率提高 2-3 倍。最近的几项研究使我们推测,利巴韦林在 AA 和 CA HCV 基因型 1 患者中的药代动力学不同,这种差异导致 PEGIFN 和利巴韦林在 AA 中的疗效较低:1) 利巴韦林剂量和利巴韦林之间存在显着相关性接受 PEGIFN 联合治疗的患者治疗期间的血清浓度和病毒学应答率; 2) 最近的 HCV RNA 动力学数学模型表明,对于 IFN 治疗效果较差的患者(如感染 HCV 基因型 1 的 AA 患者),利巴韦林治疗对于 HCV 清除更为重要; 3) Brennan 等人的一项试点研究。发现与 CA HCV 患者相比,AA 患者的利巴韦林清除率增加且利巴韦林血清水平较低。该项目的长期目标是缩小 AA 和 CA 之间 HCV 治疗效果的差异。该项目有 2 个具体目标:1) 在 Virahep-C 研究中,确定 PEGIFN alfa-2a 和利巴韦林治疗期间 AA 和 CA HCV 基因型 1 患者的利巴韦林血浆水平与病毒学反应和贫血之间的关系; 2) 确定感染 HCV 基因型 1 的 AA 和 CA 中利巴韦林的药代动力学。 PEGIFN 和利巴韦林或利巴韦林样药物很可能仍将是未来 HCV 治疗(包括 HCV 聚合酶和蛋白酶抑制剂)的组成部分。本研究的结果将阐明利巴韦林药代动力学在PEGIFN和利巴韦林治疗期间的重要性,有助于优化利巴韦林剂量,并最终提高HCV基因1型治疗AA和CA患者的疗效。这项拟议的研究旨在提高感染基因 1 型病毒(对治疗最有抵抗力)的非裔美国人中慢性丙型肝炎 (HCV) 的现有疗法的疗效。需要更有效的治疗方法来减少非裔美国人和白人美国人在丙肝病毒肝病相关疾病和死亡方面的差异。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Population pharmacokinetics and pharmacodynamics of ribavirin in patients with chronic hepatitis C genotype 1 infection.
利巴韦林在基因1型慢性丙型肝炎感染患者中的群体药代动力学和药效学。
- DOI:
- 发表时间:2012-09
- 期刊:
- 影响因子:0
- 作者:Jin, Runyan;Fossler, Michael J;McHutchison, John G;Howell, Charles D;Dowling, Thomas C
- 通讯作者:Dowling, Thomas C
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CHARLES D HOWELL其他文献
CHARLES D HOWELL的其他文献
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{{ truncateString('CHARLES D HOWELL', 18)}}的其他基金
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 - 财政年份:2009
- 资助金额:
$ 18.19万 - 项目类别:
Ribavirin Pharmacokinetics, Race and HCV Treatment
利巴韦林药代动力学、种族和 HCV 治疗
- 批准号:
7242435 - 财政年份:2007
- 资助金额:
$ 18.19万 - 项目类别:
STUDY OF VIRAL RESISTANCE TO ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C (VIRAHEP)
慢性丙型肝炎 (VIRAHEP) 病毒抗病毒治疗的研究
- 批准号:
7376926 - 财政年份:2006
- 资助金额:
$ 18.19万 - 项目类别:
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