Pimecrolimus – an anti‐inflammatory drug targeting the skin

Abstract

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 antiinflammatory 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.

Evaluation of the atrophogenic potential of hydrocortisone 1% cream and pimecrolimus 1% cream in uninvolved forehead skin of patients with atopic dermatitis using optical coherence tomography

“…Its mode of action is more selective than corticosteroids, and it was shown that pimecrolimus decreases significantly microcirculation and transepidermal water loss, whereas skin hydration increases in patients with AD (13). Topically pimecrolimus is generally well tolerated even on sensitive skin areas such as the face and neck (14)(15)(16). Intermittent treatment of AD with PIM at first signs and symptoms allows an effective control of the disease and reduces the need for TCS (17,18).…”

Binding of Pimecrolimus and Tacrolimus to Skin and Plasma Proteins: Implications for Systemic Exposure after Topical Application

“…Despite a high degree of structural similarity ( Fig. 1), pimecrolimus and tacrolimus display characteristic differences in terms of pharmacological profile (Stuetz et al, 2001;Meingassner et al, 2003;Grassberger et al, 2004;Bavandi et al, 2006;Kalthoff et al, 2007), and physicochemical and pharmacokinetic properties. Regarding physicochemical properties, the higher lipophilicity of pimecrolimus is noteworthy: pimecrolimus features an 8-fold higher octanol-water distribution coefficient than tacrolimus (Billich et al, 2004).…”

The use of calcineurin inhibitors in atopic dermatitis

“…A bőrben vagy a keringésben nem raktározódik el, így sem rövid, sem hosszú távon nincs szisztémás hatása. A pimecrolimus a helyi kortikoszteroidokkal és a tacrolimussal hasonló mértékben penetrál a bőrbe, szisztémás hatás lehetősége gyulladt bőrön történő alkalmazás esetén is minimális (10).…”