Intranasal treatment of cowpox virus respiratory infections in mice with cidofovir

Orthopoxvirus infections in mice have been effectively treated with cidofovir, a clinically approved drug given by intravenous infusion to treat cytomegalovirus infections. In a bioterrorist scenario it would be technically difficult to give this drug to a large number of exposed individuals. New tr...

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Veröffentlicht in:Antiviral research 2000-09, Vol.47 (3), p.171-177
Hauptverfasser: Smee, Donald F, Bailey, Kevin W, Wong, Min-Hui, Sidwell, Robert W
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creator Smee, Donald F
Bailey, Kevin W
Wong, Min-Hui
Sidwell, Robert W
description Orthopoxvirus infections in mice have been effectively treated with cidofovir, a clinically approved drug given by intravenous infusion to treat cytomegalovirus infections. In a bioterrorist scenario it would be technically difficult to give this drug to a large number of exposed individuals. New treatment approaches are being sought, which include giving cidofovir by alternative routes or designing oral prodrugs of cidofovir. In this report, intranasal cidofovir was investigated as a treatment of pulmonary cowpox virus infections in BALB/c mice. Ninety to 100% of animals given a single intranasal drug treatment (10, 20 or 40 mg/kg) 24 h after virus challenge survived the infection, whereas all placebo-treated mice died. Doses of 2.5 and 5 mg/kg resulted in 60 and 80% survival, respectively. Single treatments of 20 and 40 mg/kg could be given up to 3 days after virus inoculation and still be 80–90% protective. A single 40 mg/kg treatment of infected mice given 1 or 2 days after infection also resulted in statistically significant decreases in virus titer in lungs and nose/sinus compared to the placebo group. Drug efficacy was found to be contingent upon treatment volume. A 10 mg/kg intranasal dose given 24 h after virus challenge was 100 and 50% effective in volumes of 40 and 20 μl, respectively. The same dose in 5 and 10 μl volumes caused no decrease in mortality. The results of these studies establish the utility of cidofovir treatment of poxvirus infections in mice by intranasal route. The data suggest the possibility that aerosol delivery of cidofovir to human lungs may be a viable alternative to intravenous dosing.
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Drug efficacy was found to be contingent upon treatment volume. A 10 mg/kg intranasal dose given 24 h after virus challenge was 100 and 50% effective in volumes of 40 and 20 μl, respectively. The same dose in 5 and 10 μl volumes caused no decrease in mortality. The results of these studies establish the utility of cidofovir treatment of poxvirus infections in mice by intranasal route. The data suggest the possibility that aerosol delivery of cidofovir to human lungs may be a viable alternative to intravenous dosing.</description><identifier>ISSN: 0166-3542</identifier><identifier>EISSN: 1872-9096</identifier><identifier>DOI: 10.1016/S0166-3542(00)00105-4</identifier><identifier>PMID: 10974369</identifier><identifier>CODEN: ARSRDR</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Administration, Intranasal ; Animals ; Antibiotics. Antiinfectious agents. 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Drug efficacy was found to be contingent upon treatment volume. A 10 mg/kg intranasal dose given 24 h after virus challenge was 100 and 50% effective in volumes of 40 and 20 μl, respectively. The same dose in 5 and 10 μl volumes caused no decrease in mortality. The results of these studies establish the utility of cidofovir treatment of poxvirus infections in mice by intranasal route. The data suggest the possibility that aerosol delivery of cidofovir to human lungs may be a viable alternative to intravenous dosing.</description><subject>Administration, Intranasal</subject><subject>Animals</subject><subject>Antibiotics. Antiinfectious agents. 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subjects Administration, Intranasal
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral
Antiviral agents
Antiviral Agents - administration & dosage
Antiviral Agents - pharmacology
Antiviral Agents - therapeutic use
Biological and medical sciences
Cercopithecus aethiops
Cidofovir
Cowpox - drug therapy
Cowpox - mortality
Cowpox - virology
Cowpox virus
Cowpox virus - drug effects
Cowpox virus - growth & development
Cytosine - administration & dosage
Cytosine - analogs & derivatives
Cytosine - pharmacology
Cytosine - therapeutic use
Female
Intranasal treatment
Medical sciences
Mice
Mice, Inbred BALB C
Organophosphonates
Organophosphorus Compounds - administration & dosage
Organophosphorus Compounds - pharmacology
Organophosphorus Compounds - therapeutic use
Pharmacology. Drug treatments
Respiratory System - drug effects
Respiratory System - virology
Respiratory Tract Infections - drug therapy
Respiratory Tract Infections - mortality
Respiratory Tract Infections - virology
Vero Cells
Viral Plaque Assay
title Intranasal treatment of cowpox virus respiratory infections in mice with cidofovir
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