Validation of an in vivo wound healing model for the quantification of pharmacological effects on epidermal regeneration.

BACKGROUND: Non-invasive assessment methods such as measurement of the transepidermal water loss (TEWL) allow a continuous follow-up of cutaneous processes with impairment of the epidermal barrier function. OBJECTIVE: The aim of the trial was to establish an in vivo model for the assessment of drug effects on epidermal regeneration. METHODS: Twenty healthy volunteers were included in this double-blind randomized trial. After setting four suction blisters on the volar aspect of the forearm, the epidermis was removed to create a standardized subepidermal wound. Thereafter the wounds were treated topically for 6 h daily during 14 days. The following treatments were to be compared: a clobetasol 17-propionate preparation under occlusion, a corticoid-free cream under occlusion, no treatment and occlusion (aluminium chamber), no treatment and no occlusion. Daily measurement of TEWL above the wounds was performed. RESULTS: The 0.05% clobetasol 17-propionate preparation caused a dramatic delay in TEWL decrease, whereby the untreated unoccluded field showed a continuous decrease over the observed period of 14 days. Occlusion and corticoid-free treatment led to a weak but significant delay of TEWL decrease when compared to the untreated unoccluded test field. CONCLUSION: This model seems to describe re-epithelialization in a reliable manner and can be used for in vivo assessment of drug effects on migrating and proliferating epithelial cells.

Activity of topically applied methylprednisolone aceponate in relation to other topical glucocorticosteroids in healthy volunteers.

Topical glucocorticosteroids are useful in the treatment of various skin diseases. Although there are already many corticosteroids available, there is still need for highly potent and well tolerated ones. The anti-inflammatory activity of methylprednisolone aceponate (MPA, CAS 86401-95-8) has been investigated in 165 healthy volunteers of either sex. UV-B irradiation or cellophane tape stripping has served to produce erythema. First, the dose response relationship of MPA ointment (0.01%, 0.05%, 0.1% and 0.5%) has been evaluated. MPA effects have been related to those of the vehicle and difluocortolone 21-valerate 0.1% (DFV) ointment. Then the activity of 0.1% MPA (cream, ointment and fatty ointment) has been related to those of the respective vehicles as well as commercially available preparations of five corticosteroids: betamethasone 17,21-dipropionate 0.64% (BDP), betamethasone 17-valerate 0.1% (BV), clobetasol 17-propionate 0.05% (CP), hydrocortisone 17-butyrate 0.1% (HCB), prednicarbate 0.25% (P). In each experiment, MPA activity significantly exceeded that of the respective vehicle (p < or = 0.05). MPA 0.01-0.5% ointment exhibited strong anti-inflammatory activity, at least corresponding to that of 0.1% DFV ointment. A dose-dependent activity could only be observed in the UV-B-erythema test using 3 fold MED (minimal erythema doses) for irradiation, a test model differentiating strong corticosteroids. The comparison of 0.1% MPA formulations with respective reference preparations showed the following results: On stripped skin no significant differences could be detected which is demonstrated in the example of cream formulations.(ABSTRACT TRUNCATED AT 250 WORDS)