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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Effect of azone and propylene glycol on penetration of trifluorothymidine through skin and efficacy of different topical formulations against cutaneous herpes simplex virus infections in guinea pigs.

Tropical formulations of 5-trifluoromethyl-2'-deoxyuridine (TFT) containing different concentrations of TFT, Azone (Nelson Research and Development, Irvine, Calif.), and propylene glycol were evaluated for their potential efficacy in the treatment of cutaneous herpes simplex virus infections by in vitro studies of TFT penetration through skin and in vivo studies of therapeutic activity against herpes simplex virus type 1 infections in the dorsal cutaneous guinea pig model. Azone dramatically increased TFT penetration through human and guinea pig skin. Unexpectedly, high concentrations of propylene glycol were also associated with increased penetration. Studies in the guinea pig model revealed increased efficacy with Azone-propylene glycol-containing formulations, consistent with the in vitro drug diffusion results. A formulation containing 1% TFT, 5% Azone, and 80% propylene glycol decreased lesion area, in comparison to the drug vehicle control, more effectively than 5% acyclovir in polyethylene glycol (reduction of 70 versus 46%, P = 0.03). These studies demonstrate the value of penetration-enhancing agents and the need for careful preclinical evaluations in the development of topical antiviral agents.[1]


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