Immunomodulatory macrolactams for topical treatment of inflammatory skin diseases.

Tacrolimus (FK-506; Fujisawa Pharmaceutical Co Ltd) and pimecrolimus (SDZ-ASM-981; Novartis AG) are topical immunomodulators, which provide an alternative to glucocorticosteroids for the topical treatment of atopic dermatitis and other inflammatory dermatoses. Both substances form a complex with cytosolic immunophilins. The complex blocks calcineurin and inhibits the transcription of NF-AT-dependent pro-inflammatory cytokine genes. Multicenter, randomized, double-blind clinical trials have shown the efficacy of both substances in atopic dermatitis. We review the physicochemical characteristics, mode of action, pharmacokinetic data, side effects, results of the clincal trials and further indications for tacrolimus and pimecrolimus.