In Vivo Influenza Virus-Inhibitory Effects of the Cyclopentane Neuraminidase Inhibitor RWJ-270201

The cyclopentane influenza virus neuraminidase inhibitor RWJ-270201 was evaluated against influenza A/NWS/33 (H1N1), A/Shangdong/09/93 (H3N2), A/Victoria/3/75 (H3N2), and B/Hong Kong/05/72 virus infections in mice. Treatment was by oral gavage twice daily for 5 days beginning 4 h pre-virus exposure. The influenza virus inhibitor oseltamivir was run in parallel, and ribavirin was included in studies with the A/Shangdong and B/Hong Kong viruses. RWJ-270201 was inhibitory to all infections using doses as low as 1 mg/kg/day. Oseltamivir was generally up to 10-fold less effective than RWJ-270201. Ribavirin was also inhibitory but was less tolerated by the mice at the 75-mg/kg/day dose used. Disease-inhibitory effects included prevention of death, lessening of decline of arterial oxygen saturation, inhibition of lung consolidation, and reduction in lung virus titers. RWJ-270201 and oseltamivir, at doses of 10 and 1 mg/kg/day each, were compared with regard to their effects on daily lung parameters in influenza A/Shangdong/09/93 virus-infected mice. Maximum virus titer inhibition was seen on day 1, with RWJ-270201 exhibiting the greater inhibitory effect, a titer reduction of >10(4) cell culture 50% infective doses (CCID(50))/g. By day 8, the lung virus titers in mice treated with RWJ-270201 had declined to 10(1.2) CCID(50)/g, whereas titers from oseltamivir-treated animals were >10(3) CCID(50)/g. Mean lung consolidation was also higher in the oseltamivir-treated animals on day 8. Both neuraminidase inhibitors were well tolerated by the mice. RWJ-270201 was nontoxic at doses as high as 1,000 mg/kg/day. These data indicate potential for the oral use of RWJ-270201 in the treatment of influenza virus infections in humans

Management of Influenza Symptoms in Healthy Adults: Cost-effectiveness of Rapid Testing and Antiviral Therapy

OBJECTIVE: To determine the cost-effectiveness of rapid diagnostic testing and empiric antiviral therapy for healthy adults with symptoms of influenza. DESIGN: Cost-effectiveness analysis using a decision model based on previously published data. Outcome measures included costs and quality-adjusted life expectancy. SETTING: Physician's office. PATIENTS/PARTICIPANTS: Hypothetically healthy, working adults < 65 years of age presenting with cough and fever during the influenza season. INTERVENTIONS: Rapid testing or clinical diagnosis followed by treatment with amantadine, rimantadine, oseltamivir, or zanamivir compared with no antiviral therapy. RESULTS: Base-case analysis: not giving antiviral therapy is the most expensive and least effective strategy, costing $471 per patient, mostly owing to time lost from work. Amantadine treatment increases life expectancy by 0.0014 quality-adjusted life years (QALYs) while saving$108 per patient relative to no antiviral therapy. Zanamivir is slightly more effective than amantadine, adding 0.0002 QALYs at an incremental cost of $31, or$133,000 per QALY saved. All other strategies, including testing strategies, are both less effective and more expensive. SENSITIVITY ANALYSIS: The model is sensitive to the probability of influenza infection, proportion of influenza caused by type B, the relative efficacy of the various drugs, and the value of a workday. At a clinical probability of influenza infection > 20%, antiviral therapy is favored. As the proportion of influenza B increases, zanamivir is favored over amantadine. Testing is rarely indicated. Ignoring the costs of lost workdays, amantadine treatment costs $1,200/QALY saved. CONCLUSIONS: Antiviral therapy with either amantadine or zanamivir is cost-effective for healthy, young patients with influenza-like illness during the influenza season, depending on the prevalence of influenza B