Influenza and Emerging Infectious Diseases

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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.