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Antimicrobial Agents and Chemotherapy, November 1999, p. 2642-2647, Vol. 43, No. 11
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Chemoprophylaxis of Influenza A Virus Infections, with Single Doses of Zanamivir, Demonstrates that Zanamivir Is Cleared Slowly from the Respiratory Tract

Robert J. Fenton,* Peter J. Morley, Ian J. Owens, David Gower, Simon Parry, Lee Crossman, and Tony Wong

Glaxo Wellcome Research and Development Ltd., Stevenage, United Kingdom

Received 14 September 1998/Returned for modification 13 November 1998/Accepted 25 August 1999

Zanamivir (4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid; Relenza; GG167) is a potent and highly specific neuraminidase (sialidase) inhibitor with inhibitory activity in vivo against both influenza A and B viruses. This compound has been extensively tested in both mouse and ferret models of influenza and has recently been approved for the treatment of influenza in Europe and Australasia. The compound markedly reduces the clinical course 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 prophylactic dose of zanamivir in addition to a therapeutic regime. The studies reported here were designed to determine the persistence of zanamivir, as assessed by its antiviral activity in vivo, in the respiratory tracts of infected animals. We have shown that the prophylactic administration of zanamivir, when the drug is given in a single dose by the intranasal route, can significantly reduce lung virus titers in the mouse and can reduce both viral titers and symptoms in the ferret. Whole-body autoradiographical analyses of mice have indicated a long retention time for this compound in respiratory 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 prophylactic agent in protecting at-risk groups from influenza virus infection. In addition, these data may be useful in the design of prophylactic protocols for humans, in that the dosing schedule may only need to be intermittent to provide protection.

* Corresponding author. Mailing address: Systems Biology, Glaxo Wellcome Research and Development, Gunnels Wood Rd., Stevenage, Hertfordshire SG1 2NY, United Kingdom. Phone: 01438 763825. Fax: 01438 763363. E-mail: RJF2376{at}glaxowellcome.co.uk.

Antimicrobial Agents and Chemotherapy, November 1999, p. 2642-2647, Vol. 43, No. 11
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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