Influenza and Emerging Infectious Diseases

在这一新项目研究的病原体中，最重要的是流感病毒，既包括传统季节性流感的病原体，也包括禽流感(H5N1)病毒的新威胁。使用现有或新开发的策略治疗感染的新方法是LIR临床研究部这一重要新项目的主要重点。该项目采取的第一项重大举措是与退伍军人事务部和国防部开展的一项协作议定书。这个多中心方案的目标是确定是否可以使用新的药代动力学方法来延长奥司他韦的有效半衰期，奥司他韦是美国和其他地方用于治疗季节性流感的主要获得许可的口服抗病毒药物，也是一种在全球范围内相对短缺的药物。具体地说，该方案检查了两种不同剂量的口服丙磺舒与单独口服奥司他韦对常规预防剂量奥司他韦的相对药代动力学的影响。丙磺舒是一种已获许可的尿酸尿剂，已知会影响某些药物的肾脏分泌。该方案是在美国4个中心的53名65岁以上和65岁以下的正常志愿者中进行的：两个DVA站点(包括作为主导中心的Palo Alto Health Care System)、一个DOD站点和NIH临床中心。奥司他韦联合丙磺舒的药代动力学最近被分析，显示后者对前者的谷值和曲线下面积都有剂量依赖性的有利影响。

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.