Pimecrolimus is the most recent member of
calcineurin inhibitors available for the
therapy for inflammatory
skin diseases. It targets T-cells and mast cells and inhibits the production and release of
cytokines and other inflammatory mediators, as well as the expression of signals essential for the activation of inflammatory T-lymphocytes.
Pimecrolimus has a cell-selective mode of action. In contrast to
corticosteroids, it does not affect, e.g., Langerhans'cells/dendritic cells (LC/DC), as demonstrated in vitro with human monocyte-derived DC and in vivo with epidermal LC in mice, nor human primary fibroblasts. As shown in vitro with human skin and by comparison of clinical pharmacokinetic data from patients with
atopic dermatitis,
pimecrolimus permeates less through skin than
tacrolimus and much less than
corticosteroids. It, thus, has a lower potential for transcutaneous resorption after
topical administration, resulting in a lower risk of systemic effects.
Pimecrolimus has high anti-inflammatory activity in animal models of skin
inflammation, including a model reflecting
neurogenic inflammation, but a more favourable balance of anti-inflammatory vs. immunosuppressive activity than
tacrolimus.
Pimecrolimus does not affect sensitization in a murine model of
allergic contact dermatitis and has a lower potency in various models of immunosuppression after systemic administration, compared to
tacrolimus. In conclusion, the results of preclinical studies show that
pimecrolimus has a selective pharmacological profile, suited for effective and safe treatment for inflammatory
skin diseases.