title: Cutaneously applied acyclovir acts systemically in the treatment of herpetic infection in the hairless mouse.
abstract: Using the SKH-1 hairless mouse (HM) we have addressed the issue as to whether topically applied acyclovir (ACV) may mediate some of its antiviral actions by a systemic effect. When topically applied in a formulation consisting of polyvinyl alcohol (25% w/v):DMSO:cremophor EL:linoleic acid (63:16:16:5, v/v/v/v), ACV penetrated hairless mouse skin in a concentration-dependent manner and dose-dependently reduced cutaneous herpes simplex virus 1 (HSV-1) KOS infection. Topically applied ACV also effectively reduced the mortality associated with disseminated HSV-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 nmoles/ml and 120 nmoles/g. At 1 h following an oral dose of ACV with antiviral efficacy comparable to topically applied ACV (1.7% w/v) the plasma and skin concentrations of ACV were 21.3 nmoles/ml and 51 nmoles/g. These findings imply that when applied topically to the HM, ACV can mediate a portion of its antiviral activity through a systemic mode of action.
authors.affiliation: Department of Pharmacology, Bio-Mega/Boehringer Ingelheim Research Inc., Laval, Que., Canada.
authors.forename: G T
authors.initials: GT
authors.lastname: Bolger
authors.forename: T
authors.initials: T
authors.lastname: Allen
authors.forename: M
authors.initials: M
authors.lastname: Garneau
authors.forename: N
authors.initials: N
authors.lastname: Lapeyre
authors.forename: F
authors.initials: F
authors.lastname: Liard
authors.forename: J
authors.initials: J
authors.lastname: Jaramillo
mesh_terms: D000212:Acyclovir / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D006561:Herpes Simplex / Q000188:drug therapy* / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D066298:In Vitro Techniques; D051379:Mice; D008812:Mice, Hairless; D012869:Skin Absorption / Q000187:drug effects; D012874:Skin Diseases, Infectious / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000212:Acyclovir