Abstract
FK506 (Tacrolimus) is a potent immunosuppressive agent and its ointment formulation was shown to be effective on atopic dermatitis in a clinical study. As atrophy of the skin is one of the adverse effects of dermal application of such drugs as glucocorticoid ointment, the aim of the present study was to investigate whether FK506 ointment induces skin atrophy in rats.
0.3% FK506 ointment treatment did not induce skin atrophy at the application site when applied daily for 3 weeks to rats. In contrast, glucocorticoid ointments such as 0.05% clobetasol 17-propionate (CP: Dermovate®), 0.12% betamethasone 17-valerate (BV; Rinderon®-V), 0.05% clobetasone 17-butyrate (CB; Kindavate®), and 0.5% prednisolone (Pr: Prednisolone) elicited skin atrophy, and histopathologically decreased subcutaneous adipose tissue, and caused thinning of the epidermis and dermis. Furthermore, staining by proliferating cell nuclear antigen (PCNA) showed that these glucocorticoid ointments led to suppression of epidermal cell proliferation, and their potency in descending manner was CP>Pr>CB>BV.
In conclusion, it was clearly established that FK506 does not induce skin atrophy, which is one of the characteristic dermal toxicities of glucocorticoid ointments. The drug is therefore expected to be well tolerated for long term application in skin deseases.
