Abstract |
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.
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Authors | Mike Bray, Mark Martinez, Deborah Kefauver, Michael West, Chad Roy |
Journal | Antiviral research
(Antiviral Res)
Vol. 54
Issue 3
Pg. 129-42
(Jun 2002)
ISSN: 0166-3542 [Print] Netherlands |
PMID | 12062386
(Publication Type: Journal Article)
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Chemical References |
- Aerosols
- Antiviral Agents
- Organophosphonates
- Organophosphorus Compounds
- Cytosine
- Cidofovir
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Topics |
- Administration, Inhalation
- Aerosols
- Animals
- Antiviral Agents
(administration & dosage, pharmacology)
- Body Weight
- Bronchopneumonia
(drug therapy, prevention & control, virology)
- Cidofovir
- Cowpox
(drug therapy, prevention & control, virology)
- Cowpox virus
(growth & development, metabolism)
- Cytosine
(administration & dosage, analogs & derivatives, pharmacology)
- Female
- Injections, Subcutaneous
- Lung
(pathology, virology)
- Mice
- Mice, Inbred BALB C
- Organ Size
- Organophosphonates
- Organophosphorus Compounds
(administration & dosage, pharmacology)
- Statistics, Nonparametric
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