CUTANEOUSLY APPLIED ACYCLOVIR ACTS SYSTEMICALLY IN THE TREATMENT OF HERPETIC INFECTION IN THE HAIRLESS MOUSE

Using the SKH-1 hairless mouse (HM) we have addressed the issue as to whether topically applied acyclovir (ACV) may mediate some of its anti viral actions by a systemic effect. When topically applied in a formul ation consisting of polyvinyl alcohol (25% w/v):DMSO:cremophor EL:lino leic acid (63:16:16:5, v/v/v/v), ACV penetrated hairless mouse skin in a concentration-dependent manner and dose-dependently reduced cutaneo us herpes simplex virus 1 (HSV-1) KOS infection. Topically applied ACV also effectively reduced the mortality associated with disseminated H SV-2 HG-52 infection. At 1 h following topical application of 1.7% w/v ACV the plasma and skin concentrations of ACV were 5.5 eta moles/ml a nd 120 eta moles/g. At 1 h following an oral dose of ACV with antivira l efficacy comparable to topically applied ACV (1.7% w/v) the plasma a nd skill concentrations of ACV were 21.3 eta moles/ml and 51 eta moles /g. These findings imply that when applied topically to the HM, ACV ca n mediate a portion of its antiviral activity through a systemic mode of action. (C) 1997 Elsevier Science B.V.