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

Abstract

Topical foscarnet (PFA) and acyclovir (ACV) were compared in the dorsal cutaneous guinea pig model of herpes simplex virus type 1 infection. The relative order of efficacy was PFA cream>ACV cream>ACV ointment. In vitro studies demonstrated that PFA and ACV formulated in cream vehicles penetrated through guinea pig skin 7-to 10-fold faster than did ACV in ointment.Foscarnet cream (sodium phosphonoformate [PFA]), acyclovir (ACV) cream, and ACV ointment are topical antiviral preparations which have received extensive clinical evaluation as treatments for recurrent herpes simplex labialis and genitalis in normal, nonimmunocompromised subjects. Modest success has been claimed for PFA cream (19,26) and ACV cream (6,7,15,25), while the majority of studies with ACV ointment in recurrent disease have failed to demonstrate any clinical benefit (3,17,20,21,24,27 (8) were 14.2 and 0.14 ,ug/ml, respectively. Sixteen Hartley strain, outbred female albino guinea pigs weighing 350 to 400 g each were inoculated with HSV-1 E115 in six different areas on the depilated dorsum by multiple shallow punctures as originally described by Hubler et al. (14). Treatment of each infection site with 200 to 250 mg of cream or ointment was begun 24 h after inoculation and continued once per day for 3 days. The frequency of dosing was limited because some formulations were irritating to the skin. This protocol allowed for 12 comparisons between each drug and its contralaterally applied vehicle as well as comparisons of efficacy between each of the four different antiviral formulations. 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 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. All probability determinations were two tailed, and a P of c 0.05 was considered to be significant.The results of the in vivo studies are shown in Table 1. Compared with lesion severity at vehicle control-treated sites, reductions of the mean number of lesions by 3% PFA, 0.3% PFA, ACV cream, and ACV ointment were 54, 36, 19, and -8%, respectively; reductions in the mean lesion area were 73, 52, 31, and 19%; and the reductions in mean lesion virus titer effected by these treatments were 90, 80, 75, and 60%. The greater reduction in number of lesions by 3% PFA, 0.3% PFA, and ACV cream compared with that of ACV ointment was statistically significant (P c 0.03). Both 3% and 0.3% PFA were significantly more effective in reducing lesion area t...

Combinations of Antiviral and Anti-Inflammatory Preparations for the Topical Treatment of Herpes Simplex Virus Assessed using a Murine Zosteriform Infection Model

“…These moderate effects on the clinical course of the disease are similar to those previously described in clinical trials of topical foscarnet for the treatment of recurrent cutaneous herpes in immuncompetent patients (Barton et al, 1986;Spruance et al, 1986). Examination of the virus titres in the ears on day 7 post-infection showed, however, that antiviral treatments significantly reduced the virus titre compared to placebo.…”

Sodium Lauryl Sulfate Increases the Efficacy of a Topical Formulation of Foscarnet against Herpes Simplex Virus Type 1 Cutaneous Lesions in Mice

“…The ED 50 of foscarnet was 74.18 M. The ED 50 decreased to 30.10, 34.40, and 55.24 M when foscarnet was combined with 12.5, 25, and 37.5 M SLS, respectively. SLS alone also exerted an inhibitory effect on the HSV-1 strain F-induced cytopathic effect, with an ED 50 of 65.30 M. The ED 50 was not modified when SLS was combined with 17 M foscarnet, but it was decreased to 32.61 and 55.35 M in the presence of 33 and 50 M foscarnet, respectively. The inhibitory effects of combinations of both compounds on the virus-induced cytopathic effect were analyzed by the isobologram method.…”

“…Foscarnet also decreased the viabilities of these cells in a concentration-dependent manner. The CC 50 of foscarnet for this cell line was 0.85% (28 mM). Thus, this cell line is susceptible to foscarnet at concentrations approximately twofold lower than those to which Vero cells are susceptible.…”

“…Foscarnet is thus effective for the treatment of acyclovir-resistant herpetic infections (25,38). However, the currently available treatments, either topical or systemic, have only moderate effects on the clinical course of recurrent herpes labialis and herpes genitalis in immunocompetent hosts (6,9,43,44,46,48,50,55).…”

Efeitos do Foscarnet sobre a infecção pelos herpesvírus bovino tipos 1 e 5 em coelhos

“…Em macacos infectados com o VZV, o PFA reduziu o período de viremia e a severidade das lesões (Öberg et al 1989). Em cobaias, este fármaco preveniu o desenvolvimento de lesões cutâneas e genitais após a inoculação com o HSV-1 (Spruance et al 1986(Spruance et al , Öberg et al 1989. O PFA também reduziu a mortalidade de camundongos infectados com o HSV-1 (Kern et al 1978(Kern et al , Öberg et al 1989.…”