Treatment of aerosolized cowpox virus infection in mice with aerosolized cidofovir.
The Brighton strain of cowpox virus causes lethal bronchopneumonia when delivered as a small-particle (1 microm) aerosol to weanling BALB/c mice. We showed previously that this disease can be prevented or cured with one subcutaneous injection of cidofovir (HPMPC, Vistide). To determine whether even better results could be obtained by delivering the drug directly to the respiratory tract, we administered cidofovir by small-particle aqueous aerosol before or after aerosolized cowpox infection. In a series of five experiments, aerosol doses of 0.5-5 mg/kg were always more effective than 25 mg/kg and sometimes more effective than 100 mg/kg injected subcutaneously, as measured by changes in body and lung weight, lung viral titers, pulmonary pathology and survival. A cyclic analog ((1-[(S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl] cytosine) (cHPMPC) was less protective. The results suggest that aerosolized cidofovir would be effective for prophylaxis or early post-exposure therapy of human smallpox or monkeypox virus infection.
Bray
Mike
M
Virology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, Frederick, MD 21702-5011, USA. mike.bray@det.amedd.army.mil
Martinez
Mark
M
Kefauver
Deborah
D
West
Michael
M
Roy
Chad
C
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001835:Body Weight; D001996:Bronchopneumonia / Q000188:drug therapy / Q000517:prevention & control / Q000821:virology; D000077404:Cidofovir; D015605:Cowpox / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D015608:Cowpox virus / Q000254:growth & development* / Q000378:metabolism; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D005260:Female; D007279:Injections, Subcutaneous; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D018709:Statistics, Nonparametric
D000336:Aerosols; D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir