Influenza and Emerging Infectious Diseases

流感和新发传染病

• 批准号: 7592336
• 负责人: Richard Davey
• 金额: $ 109.44万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7592336
• 关键词: Affect; Age-Years; Antiviral Agents; Area Under Curve; Birds; Clinical; Clinical Research; Department of Defense; Dose; Drug Kinetics; Drug usage; Emerging Communicable Diseases; Goals; Half-Life; Healthcare Systems; Human; Immunologics; Infection; Influenza; Influenza A Virus, H5N1 Subtype; Kidney; Lead; Licensing; Oral; Oseltamivir; Pharmaceutical Preparations; Population; Probenecid; Protocols documentation; Public Health; Relative (related person); Risk; Site; United States; United States National Institutes of Health; Uricosuric Agents; Veterans; improved; influenzavirus; novel; pathogen; prevent; prophylactic; volunteer

Foremost among the pathogens under study in this new project is the influenza virus, including both the agent of conventional seasonal influenza as well as the emerging threat of avian (H5N1) virus. Novel means to treat infection with either agent using existing or newly developed strategies are a primary focus of this important new project within the Clinical Research Section of the LIR. The first major initiative undertaken in this project has been a collaborative protocol undertaken with the Department of Veterans Affairs (DVA) as well as the Department of Defense. The goal of this multi-center protocol was to determine if novel pharmacokinetic means could be used to extend the useful half-life of oseltamivir, the major licensed oral antiviral drug used to treat seasonal influenza in the United states and elsewhere and also a drug in comparatively short supply on a global scale. Specifically, the protocol examined the effect of two different doses of oral probenecid, a licensed uricosuric agent known to affect the renal secretion of certain drugs, on the relative pharmacokinetics of conventional prophylactic doses of oral oseltamivir compared to oral oseltamivir alone. This protocol was conducted in 53 normal volunteers above and below 65 years of age at 4 centers in the United States: two DVA sites (including the Palo Alto Health Care system as lead center), one DOD site, and the NIH Clinical Center. The pharmacokinetics of oseltamvir plus probenecid have recently been analyzed and show a dose-dependent favorable effect of the latter upon both the trough and area-under-the-curve concentrations of the former.

在这个新项目中所研究的病原体中，最重要的是流感病毒，包括传统季节性流感的药物以及鸟类（H5N1）病毒的新兴威胁。使用现有策略或新开发策略治疗特工的新型方法是LIR临床研究部分中这个重要新项目的主要重点。该项目中采取的第一项主要倡议是与退伍军人事务部（DVA）以及国防部进行的合作协议。该多中心协议的目的是确定新型的药代动力学手段是否可以用于扩展奥斯塔米维尔的有用半衰期，奥斯塔米维尔是用于治疗美国和其他地方的季节性流感的主要许可的口服抗病毒药物，以及在全球范围内相对较短的供应中的药物。具体而言，该方案检查了两种不同剂量的口服概率（一种已知会影响某些药物肾分泌的许可的犹太毒素的影响）对与单独口服oseltamivir相比，对某些药物的肾脏分泌对常规预防性oseltamivir的相对药代动力学的影响。该方案是在美国4个中心以上和65岁以上的53名正常志愿者中进行的：两个DVA站点（包括帕洛阿尔托医疗保健系统作为铅中心），一个DOD站点和NIH临床中心。最近已经分析了Oseltamvir Plus ProbEnecid的药代动力学，并显示后者对前者的低谷和面积浓度的剂量依赖性效果。