1. Efficacy of CMX001 against herpes simplex virus infections in mice and correlations with drug distribution studies.
- Author
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Quenelle DC, Lampert B, Collins DJ, Rice TL, Painter GR, and Kern ER
- Subjects
- Administration, Oral, Animals, Cytosine administration & dosage, Cytosine pharmacokinetics, Disease Models, Animal, Drug Evaluation, Preclinical, Female, Mice, Mice, Inbred BALB C, Tissue Distribution, Antiviral Agents administration & dosage, Antiviral Agents pharmacokinetics, Cytosine analogs & derivatives, Herpes Simplex drug therapy, Herpesvirus 1, Human, Herpesvirus 2, Human, Organophosphonates administration & dosage, Organophosphonates pharmacokinetics
- Abstract
CMX001, an orally active lipid conjugate of cidofovir, is 50 times more active in vitro against herpes simplex virus (HSV) replication than acyclovir or cidofovir. These studies compared the efficacy of CMX001 to acyclovir in BALB/c mice inoculated intranasally with HSV types 1 or 2. CMX001 was effective in reducing mortality using doses of 5 to 1.25 mg/kg administered orally once daily, even when treatments were delayed 48-72 h post viral inoculation. Organ samples obtained from mice treated with CMX001 had titers 3-5 log(10) plaque-forming units per gram of tissue lower than samples obtained from mice treated with acyclovir, including 5 different regions of the brain. Detectable concentrations of drug-related radioactivity were documented in the central nervous system of mice after oral administration of (14)C-CMX001. These studies indicate that CMX001 penetrates the blood-brain barrier, is a potent inhibitor of HSV replication in disseminated infections and central nervous system infections, and is superior to acyclovir.
- Published
- 2010
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