Abstract
We utilized BALB/c mice infected with murine CMV (MCMV) or severe combined immunodeficient (SCID) mice implanted with human fetal tissue and infected with HCMV to determine the efficacy of (S)-9-[3-hydroxy-2-(phophonomethoxy)propyl]adenine ((S)-HPMPA), hexadecyloxypropyl-(S)-HPMPA (HDP-(S)-HPMPA) or octadecyloxyethyl-(S)-HPMPA (ODE-(S)-HPMPA). In MCMV-infected BALB/c mice, oral HDP-(S)-HPMPA at 30 mg/kg significantly reduced mortality when started 24-48 h post inoculation. In the experimental HCMV infection, oral administration of vehicle or 10mg/kg of (S)-HPMPA, HDP-(S)-HPMPA or ODE-(S)-HPMPA was initiated 24h after infection and continued for 28 consecutive days. Cidofovir (CDV), at 20mg/kg given i.p., was used as a positive control. HDP-(S)-HPMPA or ODE-(S)-HPMPA significantly reduced viral replication compared to vehicle-treated mice, while oral (S)-HPMPA was ineffective.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adenine / administration & dosage
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Adenine / analogs & derivatives*
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Adenine / pharmacology
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Adenine / therapeutic use
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Administration, Oral
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Animals
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Antiviral Agents / administration & dosage
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Antiviral Agents / pharmacology
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Antiviral Agents / therapeutic use*
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Cidofovir
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Cytomegalovirus / drug effects
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Cytomegalovirus Infections / drug therapy*
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Cytosine / administration & dosage
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Cytosine / analogs & derivatives
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Cytosine / therapeutic use
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Herpesviridae Infections / drug therapy*
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Liver / virology
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Mice
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Mice, Inbred BALB C
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Mice, SCID
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Muromegalovirus / drug effects
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Organophosphonates / administration & dosage
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Organophosphonates / pharmacology
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Organophosphonates / therapeutic use*
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Survival Analysis
Substances
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Antiviral Agents
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Organophosphonates
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octadecyloxyethyl 9-(3-hydroxy-2-(phosphonomethoxy)propyl)adenine
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Cytosine
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9-(S)-(3-hydroxy-2-(phosphonomethoxy)propyl)adenine
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Adenine
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Cidofovir
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hexadecyloxypropyl 9-(2-(phosphonomethoxy)propyl)adenine