Controlled (trans) dermal delivery of an antiviral agent (acyclovir). I: An in vivo animal model for efficacy evaluation in cutaneous HSV-1 infections

Relationship of Skin Target Site Free Drug Concentration (C*) to the In Vivo Efficacy: An Extensive Evaluation of the Predictive Value of the C* Concept Using Acyclovir as a Model Drug

“…The lesions were scored on the fifth day, and the efficacies were calculated as described earlier. 1 Our results indicate that, for a variety of formulations over a wide range of efficacies, the predictions based on C* are in good agreement with the observed in vivo efficacies. These findings strongly demonstrate the predictive value of C* over the entire range of topical efficacy, thereby further strengthening its potential for future studies.…”

“…The roto-tool allowed a better control over the length and depth of the skin abrasion compared with the needle used in earlier method. 1 The abrasion area was inoculated with HSV-1 virus, a Velcro jacket was applied over each animal, and the animals were caged individually. On the second day, 20 µL of the formulation was applied onto a rectangular skin site (2 cm 2 in area; ∼1 cm dorsal to the virus inoculation site) in the predicted path of the lesion development.…”

“…Cutaneous HSV-1 infections in hairless mice induce band-shaped skin lesions that, upon proper scoring, may be used to quantitatively calculate the antiviral drug efficacy. 1 This model was used to establish a relationship between the ACV flux delivered from transdermal patches and the resulting in vivo efficacies. 2,3 The steady-state concentration profile of ACV following a topical application is schematically represented in Figure 1.…”

“…[1][2][3][4][5] The parameter C* was proposed to be a true measure of the in vivo efficacy of a topical formualtion. We have used acyclovir (ACV) as a model drug in the treatment of cutaneous herpes simplex virus type 1 (HSV-1) infections in hairless mice to develop and substantiate this concept.…”

Influence of the treatment protocol upon the in vivo efficacy of cidofovir (HPMPC) and of acyclovir (ACV) formulations in topical treatment of cutaneous HSV‐1 infection in hairless mice

“…Treatment was initiated on various days ranging from day -6 to day 4, as outlined in Table 1. The lesions were scored on day 5 as previously described, 9 and the antiviral efficacies were calculated using the following equations: 1 where NTh, NSt, NJ, NNR, and NM are the number of animals corresponding to each of the five lesion categories and represent the cases where the lesion passes through (Th), stops (St) at the edge of, jumps (J) over, does not reach (NR), or misses (M) the treatment area, respectively.…”