Alternative Oseltamivir Dosing Strategies

Pandemic influenza infection has the potential for causing significant morbidity and mortality in the United States and elsewhere. Oseltamivir (Tamiflu\[R\]) is a selective inhibitor of influenza virus neuraminidase and is U.S. FDA approved for both treatment and prophylaxis against influenza A and B viruses. However, at a time of national emergency, the supply of oseltamivir may be limited and alternative dosing strategies may be needed in order to provide as wide protection as possible from influenza or to treat as many infected patients as possible. Agents such as Probenecid that may extend the half-life of oseltamivir while maintaining effective oseltamivir plasma levels may potentially be useful in this regard. In this multi-center, three-arm, open-label, 48 patient trial, we propose to explore the relative safety and pharmacokinetics of oseltamivir plus Probenecid for 14 days in normal volunteers above and below the age of 65, according to the following dosing strategies: 16 subjects will be assigned to Group I Control Arm (Tamiflu\[R\] 75 mg given orally once daily), 16 subjects will be assigned to Group II Treatment Arm (Tamiflu \[R\] 75 mg orally once every other day plus Probenecid 500 mg orally four times daily), and 16 subjects will be assigned to Group III Treatment Arm (Tamiflu\[R\] 75 mg orally every other day and Probenecid 500 mg orally twice daily).