CORRELATION OF IN-VIVO TOPICAL EFFICACIES WITH IN-VITRO PREDICTIONS USING ACYCLOVIR FORMULATIONS IN THE TREATMENT OF CUTANEOUS HSV-1 INFECTIONS IN HAIRLESS MICE - AN EVALUATION OF THE PREDICTIVE VALUE OF THE C-ASTERISK CONCEPT

The purpose of this study was to carry out an extensive examination of the C concept for prediction of the topical antiviral efficacies of acyclovir (ACV) formulations in a hairless mouse model for the treatme nt of cutaneous herpes simplex virus type-1 (HSV-1) infections. This m ethod is based on estimation of the free drug concentration at the tar get site (C), which is presumed to be the basal cell layer of the epi dermis. Five different formulations (containing 5% ACV) were examined in a finite dose multiple dosing regimen (twice a day application) to simulate the clinical situation. For determination of C, in vitro ACV fluxes across the hairless mouse skin were measured in an in vivo-in vitro experimental design that approximated the in vivo antiviral trea tment protocol, Then, the in vivo antiviral efficacies were measured u sing a 1-day delayed (after HSV-1 virus inoculation) 4-day treatment p rotocol. 10 mu L/cm(2) dose of ACV formulation was applied every 12 h for 4 days after which the lesions were scored and efficacies were cal culated. Our results indicate that, over a wide range of efficacies, t he predictions based on C (estimated from the experimental fluxes) ar e in good agreement with the in vivo antiviral efficacies, These studi es, therefore, support the validity of the C concept for various ACV formulations and suggest that the C approach has potential for future practical situations.