Pimecrolimus – an anti‐inflammatory drug targeting the skin

皮密莫司 他克莫司 钙调神经磷酸酶 医学 特应性皮炎 药理学 过敏性接触性皮炎 免疫学 炎症 全身给药 体内 敏化 人体皮肤 促炎细胞因子 过敏 移植 生物 内科学 生物技术 遗传学
作者
Maximilian A. Grassberger,Martin Steinhoff,D. Schneider,Thomas A. Luger
出处
期刊:Experimental Dermatology [Wiley]
卷期号:13 (12): 721-730 被引量:112
标识
DOI:10.1111/j.0906-6705.2004.00269.x
摘要

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 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.
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