Comparison of topically applied 5-ethyl-2'-deoxyuridine and acyclovir in the treatment of cutaneous herpes simplex virus infection in guinea pigs

Abstract

Three percent 5-ethyl-2'-deoxyuridine (EdU) in an aqueous cream base was compared with 5% acyclovir (ACV) in polyethylene glycol ointment and 3% EdU in 95% dimethyl sulfoxide (DMSO) for efficacy in the topical treatment of an experimental dorsal cutaneous herpes simplex virus type 1 infection in guinea pigs. Topical ACV treatment reduced the mean lesion number by 15%, the lesion area by 32%, and the lesion virus titer by 60% when compared with measurements at contralateral sites treated with the vehicle alone. Application of 3% EdU cream was more beneficial, effecting reductions of 29, 44, and 68% in the same measurements. EdU in DMSO was even more effective, reducing the lesion measurements by 39, 60, and 90%, respectively. The penetration of EdU and ACV through guinea pig skin was compared in single-chamber diffusion cells. In the aqueous cream, EdU readily penetrated excised skin and exhibited rates of flux 10-fold greater than those shown by ACV in ointment formnulation (0.56 versus 0.05 pg/cm2 per h; P = 0.05). The flux of EdU in DMSO was 3.39 jig/cm2 per h, six times higher than the flux in the cream vehicle. EdU was more effective than ACV in this experimental animal model, most likely due to better percutaneous drug delivery of EdU from the cream and DMSO vehicles.The activity of 5-ethyl-2'-deoxyuridine (EdU) against infection with herpes simplex virus (HSV) was first recognized in 1967 (13). In vitro testing by reduction in cytopathic effect has identified the mean 50% inhibitory dose against HSV type 1 (HSV-1) and HSV type 2 (HSV-2) to be 0.3 to 0.5

Comparison of foscarnet cream, acyclovir cream, and acyclovir ointment in the topical treatment of experimental cutaneous herpes simplex virus type 1 infection

“…The minimal efficacy of topical ACV ointment in the present studies (19% reduction in lesion area) and in other experiments (8,22,23) parallels the disappointing results with this preparation in recurrent cutaneous human HSV infections in normal hosts (3,17,20,21,24,27). Similarly, the better results (31 to 73% reduction in lesion area) seen with topical PFA and topical ACV cream in our model system find parallels in the recent clinical reports which indicate that these formulations may be more effective than ACV ointment (6,7,15,19,(25)(26)(27).…”

“…Further details of these procedures have been previously described (8,22 Drug flux was determined from a steady-state plot of drug concentration versus time. Further details of these procedures are available elsewhere (8,22,23).Lesion severity between drug and vehicle control-treated sites were compared by the Wilcoxon signed-rank test. The percent efficacies of different drug formulations were compared by the Mann-Whitney rank-sum procedure and in vitro flux values by Student's t test.…”

“…Further details of these procedures have been previously described (8,22 Drug flux was determined from a steady-state plot of drug concentration versus time. Further details of these procedures are available elsewhere (8,22,23).…”

“…The severity of the infection at each treatment site was evaluated on the day after completion of the treatment regimen by examining the number of lesions, the diameter of lesions, the total lesion area, and the quantity of virus in excised skin. Further details of these procedures have been previously described (8,22 Full-thickness dorsal guinea pig skin was excised, and a portion of the skin was clamped across a Franz singlechambered glass diffusion cell (Crown Glass Co., Sommerville, N.J. (8,22,23).…”

Antiviral activity of 5-ethyl-2'-deoxyuridine against herpes simplex viruses in cell culture, mice, and guinea pigs

“…The compound is also active in rabbits with herpes keratitis (13,15), in mice with systemic herpetic infection (7,8), and in dorsally infected guinea pigs (46). Studies in humans have indicated positive effects with this drug for the treatment of ocular herpes (13,35).…”