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Treatment of aerosolized cowpox virus infection in mice with aerosolized cidofovir.

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.
AuthorsMike Bray, Mark Martinez, Deborah Kefauver, Michael West, Chad Roy
JournalAntiviral research (Antiviral Res) Vol. 54 Issue 3 Pg. 129-42 (Jun 2002) ISSN: 0166-3542 [Print] Netherlands
PMID12062386 (Publication Type: Journal Article)
Chemical References
  • Aerosols
  • Antiviral Agents
  • Organophosphonates
  • Organophosphorus Compounds
  • Cytosine
  • Cidofovir
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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