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.