Treatment of primary acute genital herpes in guinea pigs by intraperitoneal administration of fluoropyrimidines

Abstract

evaluated for their efficacies in the treatment of genital infections with herpes simplex virus type 2 in guinea pigs. Intraperitoneal administration of these drugs in daily doses of 100 mg/kg of body weight initiated 24 h after virus inoculation and repeated 2 successive days thereafter inhibited development of genital lesions and reduced shedding of virus without evoking untoward reactions. In a comparative study with this 3-day dosage schedule, the efficacy of dgily doses of 50 mg of FMAU per kg was greater than that of the same doses of FIAC and FIAU, in that order; all these were more effective than daily doses of 50, 100, or 200 mg of acyclovir or of 500 mg of phosphonoformic acid per kg. These differences in efficacy were enhanced when treatment was delayed for 2 to 3 days after inoculation., and FMAU [1-(2'-deoxy-2'-fluoro-13-Darabinofuranosyl)-5-methyluracil] inhibit herpes simplex type 1 (HSV-1) and HSV-2 replication in cell culture (20; J. J. Fox, 185th Am. Chem. Soc. Natl. Meet., Seattle, Wash., 1983). FIAC and FMAU are equally active against HSV-1 and HSV-2 strains and have about the same potency as acyclovir (ACV) when assayed in rabbit kidney cells (2, 17). FIAU and FMAU are more active than ACV in the treatment of HSV encephalitis in mice (13). Topical application of FIAC and FMAU is also effective in the treatment of ocular infections in rabbits (17,18).Previous studies have shown that guinea pigs inoculated intravaginally with HSV-2 develop lesions of the external genitalia which follow a clinical course similar to that of herpes infections in human females; furthermore, this experimental infection may be used to evaluate the efficacy of various antiviral agents (8,14,16). Effective ACV and phosphonoformic acid (PFA) treatment of genital herpes in guinea pigs is well documented (1,4,6,10 laboratory (6, 10, 22) and is comparable to those used in other studies (8,14).Drug administration. All of the compounds were provided through the Antiviral Substances

Activity of 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodouracil against simian varicella virus infections in African green monkeys

“…No evidence for a mutagenic or oncogenic effect was demonstrated. The reported studies in mice and guinea pigs inoculated with HSV-1 or HSV-2 did not show any evidence of toxicity (6,9,13). Our studies in monkeys also showed no evidence of toxicity either grossly or indicated in hematology and clinical chemistry tests performed during the period of treatment.…”

“…Guinea pigs inoculated intravaginally with HSV-2 and treated with daily intraperitoneal injections of FIAC, FIAU, or FMAU at 100 mg/kg had reduced mean lesion scores on days 3, 4, 7, and 10 postinfection and a lower titer of virus shed from the vaginal tract on day 4 postinfection (6). FMAU was more effective than either FIAC or FIAU in reducing mean lesion scores when intraperitoneal treatment with the drugs at 50 mg/kg was begun either 24 or 48 h after virus inoculation.…”

Xylotubercidin against herpes simplex virus type 2 in mice

“…Candidate antiviral drugs that have proven to be effective against HSV-2 infections in animal models and that therefore seem worth pursuing for their potential in the treatment of genital herpes and HSV-2 infections in general include cyclaradine (43) as well as its predecessor vidarabine (34); the 1-(2'-deoxy-2'-fluoro-p-D-arabinofuranosyl)pyrimidine derivatives FMAU, FIAC, and FIAU (27,28); 5-ethyl-2'-deoxyuridine (EDU) (39); phosphonoformate (1,23,24,28); and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (21), particularly when combined with interferon (18)(19)(20). Cyclaradine, vidarabine, and phosphonoformate thereby offer the advan-* Corresponding author.…”