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J Infect Dis. 2010 Nov 15;202(10):1492-9. doi: 10.1086/656717. Epub 2010 Oct 5.

Efficacy of CMX001 against herpes simplex virus infections in mice and correlations with drug distribution studies.

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  • 1The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama 35233-1711, USA. dquenelle@peds.uab.edu

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.

PMID:
20923374
[PubMed - indexed for MEDLINE]
PMCID:
PMC2957530
Free PMC Article
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