Pimecrolimus (Elidel, SDZ ASM 981)--preclinical pharmacologic profile and skin selectivity

• Published in: Seminars in cutaneous medicine and surgery Vol. 20; no. 4; p. 233
• Main Authors: Stuetz, A, Grassberger, M, Meingassner, J G
• Format: Journal Article
• Language: English
• Published: United States 01.12.2001
• Subjects: Administration, Cutaneous; Animals; Cytokines - metabolism; Disease Models, Animal; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - pharmacology; In Vitro Techniques; Skin - drug effects; Tacrolimus - administration & dosage; Tacrolimus - analogs & derivatives; Tacrolimus - pharmacology
• ISSN: 1085-5629
• DOI: 10.1053/sder.2001.29066

The ascomycin macrolactam derivative pimecrolimus (Elidel, SDZ ASM 981; Novartis Pharma AG, Basel Switzerland) is a cell-selective inhibitor of inflammatory cytokines specifically developed for the treatment of inflammatory skin diseases, such as atopic dermatitis, allergic contact dermatitis, irritant contact dermatitis, and plaque-type psoriasis. It inhibits the production of inflammatory cytokines in T cells and mast cells and prevents the release of preformed inflammatory mediators from mast cells. Topically administered pimecrolimus is as effective as the high-potency corticosteroid clobetasol-17-propionate in a pig model of allergic contact dermatitis (ACD). Unlike clobetasol, however, it does not cause skin atrophy. Given orally, pimecrolimus is as potent or superior to tacrolimus (FK 506) in treating ACD in mice and rats. Pimecrolimus also effectively reduces skin inflammation and pruritus in hypomagnesemic hairless rats, a model that mimics acute signs of atopic dermatitis. Pimecrolimus shows only a low potential to impair systemic immune responses when compared with tacrolimus as shown in rats in (1) the localized graft-versus-host reaction, (2) the antibody formation to sheep red blood cells, and (3) kidney transplantation. Pimecrolimus permeates through pig skin in vitro at a 10-times lower rate than tacrolimus, indicating a lower potential for percutaneous absorption in vivo. The data suggest that pimecrolimus combines high anti-inflammatory activity in the skin with a low potential to impair systemic immune reactions.