Chemoprophylaxis of influenza A virus infections, with single doses of zanamivir, demonstrates that zanamivir is cleared slowly from the respiratory tract

Zanamivir (4-guanidino-2,4-dideoxy-2,3 dehydro-N-acetylneuraminic acid; Rel enza; GG167) is a potent and highly specific neuraminidase (sialidase) inhi bitor with inhibitory activity in vivo against both influenza A and B virus es. This compound has been extensively tested in both mouse and ferret mode ls of influenza and has recently been approved for the treatment of influen za in Europe and Australasia. The compound markedly reduces the clinical co urse of disease in humans when given therapeutically by inhalation directly into the respiratory tract. In addition, experimental influenza infections in phase I clinical trials have shown the benefit of giving a single proph ylactic dose of zanamivir in addition to a therapeutic regime. The studies reported here were designed to determine the persistence of zanamivir, as a ssessed by its antiviral activity in vivo, in the respiratory tracts of inf ected animals. We have shown that the prophylactic administration of zanami vir, when the drug is given in a single dose by the intranasal route, can s ignificantly reduce lung virus titers in the mouse and can reduce both vira l titers and symptoms in the ferret. Whole-body autoradiographical analyses of mice have indicated a long retention time for this compound in respirat ory tract tissues when it is given in a single dose by the intranasal route . These results indicate that zanamivir may have clinical value as a prophy lactic agent in protecting at-risk groups from influenza virus infection. I n addition, these data may be useful in the design of prophylactic protocol s for humans, in that the dosing schedule may only need to be intermittent to provide protection.