Combined chemotherapy of cutaneous herpes simplex infection of the guinea pig

Abstract

Cutaneous infection of guinea pigs with HSV1 was topically treated from 2 to 6 days post infection with 7 antiherpetic substances. Phosphonoformic acid and acyclovir were found to be highly effective; trifluorothymidine, thymine arabinoside, ethyldeoxyuridine, and adenine arabinoside monophosphate all had some therapeutic effect in decreasing order, whereas iododeoxyuridine was ineffective. The efficacy of treatment was evaluated from cutaneous lesion scores by the Wilcoxon rank test. The substances were combined in marginally effective concentrations. From the 21 combinations, acyclovir + phosphonoformic acid, acyclovir + thymine arabinoside, and phosphonoformic acid + thymine arabinoside suggested a synergistic interaction, which appeared significant for acyclovir + phosphonoformic acid.

Therapeutic effect of (E)‐5‐(2‐bromovinyl)‐2′‐deoxyuridine, caffeic acid oxidation product, and trisodiumphosphonoformate on cutaneous herpes simplex virus type 1 infection in guinea pigs

“…An advantage of the infection produced by this method is its characteristic biphasic course, eg, the occurrence of vesicles at the inoculation spots, followed by the appearance of satellites probably owing to a lateral spread of the virus in the skin. Hitherto these symptoms could only be induced with a steer-needle gun used for virus inoculation by Hubler et a1 [1974] and Burkhardt and Wigand [1983]. This course of infection enables a qualitative estimation of the effectiveness of antiviral substances in vivo.…”

“…The onset of incrustation, duration of the healing, as well as the beginning and duration of the satellite stage did not differ between treated and control animals. In contrast to as well as Burkhardt and Wigand [1983], these time criteria were not used for the interpretation of the results.…”

“…When the treatment was started 15 minutes after virus inoculation, 0.5% T P F inhibited the infection of the animals. This superior topical effectiveness of TPF on the primary herpes virus infection in animal models corresponds to the literature [ Burkhardt and Wigand, 1983;Helgstrand et al, 1980;Oberg et al, 1982;Oberg, 19831. At 8 hours after virus inoculation only T P F treatment was effective against the virus infection. A treatment with 0.5% TPF ointment was sufficient to inhibit completely the formation of any herpetic lesion.…”

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

“…EdU was similar in efficacy to vidarabine parenterally in the treatment of HSV encephalitis in mice (7) and topically in the cutaneous HSV infection model in athymic nude mice (10). In both athymic mice and guinea pigs, however, topical acyclovir (ACV) was more effective than EdU (5,10).…”