Penetration of guinea pig skin by acyclovir in different vehicles and correlation with the efficacy of topical therapy of experimental cutaneous herpes simplex virus infection

Abstract

Inadequate penetration of antiviral agents through the stratum corneum of the skin may be one of the limiting factors in the topical therapy of recurrent cutaneous herpes simplex virus infections in humans. In vitro studies of the penetration of the nucleoside analog acyclovir (ACV) through guinea pig skin demonstrated a marked increase in drug flux when ACV was formulated in dimethyl sulfoxide (DMSO), compared with water or polyethylene glycol (PEG) as the vehicle. To examine whether the increased transcutaneous flux of ACV effected by DMSO was meaningful in vivo, topical 5% ACV in DMSO was evaluated for the treatment of cutaneous herpes simplex virus infection in guinea pigs and compared with topical 5% ACV in PEG. When compared with infection sites treated with the vehicle alone, ACV in DMSO produced a greater percent reduction than did ACV in PEG in median lesion number (8 versus 58%; P less than 0.001), median lesion area (35 versus 73%; P = 0.001), and median lesion virus titer (21 versus 84%; P = 0.08). We conclude that DMSO is a highly effective vehicle for topical administration of ACV and is superior to PEG in our model. Careful choice of vehicle and consideration of transcutaneous penetration may be important for realization of the full potential of topical antiviral therapy in humans.