| Indication | For treatment of mild to moderate atopic dermatitis. |
| Pharmacodynamics | Pimecrolimus is a chemical that is used to treat atopic dermatitis (eczema). Atopic dermatitis is a skin condition characterized by redness, itching, scaling and inflammation of the skin. The cause of atopic dermatitis is not known; however, scientists believe that it may be due to activation of the immune system by various environmental or emotional triggers. Scientists do not know exactly how pimecrolimus reduces the manifestations of atopic dermatitis, but pimecrolimus reduces the action of T-cells and mast cells which are part of the immune system and contribute to responses of the immune system. Pimecrolimus prevents the activation of T-cells by blocking the effects of chemicals (cytokines) released by the body that stimulate T-cells. Pimecrolimus also reduces the ability of mast cells to release chemicals that promote inflammation. |
| Mechanism of action | Pimecrolimus binds with high affinity to macrophilin-12 (FKBP-12) and inhibits the calcium-dependent phosphatase, calcineurin. As a consequence, it inhibits T cell activation by blocking the transcription of early cytokines. In particular, pimecrolimus inhibits at nanomolar concentrations Interleukin-2 and interferon gamma (Th1-type) and Interleukin-4 and Interleukin-10 (Th2-type) cytokine synthesis in human T cells. Also, pimecrolimus prevents the release of inflammatory cytokines and mediators from mast cells in vitro after stimulation by antigen/lgE. |
| Absorption | Because of the low systemic absorption of pimecrolimus following topical application the calculation of standard pharmacokinetic measures such as AUC, Cmax, half-life, etc. cannot be reliably done. |
| Volume of distribution | Not Available |
| Protein binding | 74%-87% (in vitro, bound to plasma proteins) |
| Metabolism | No drug metabolism was observed in human skin in vitro. Oral administration yielded metabolites produced from O-demethylation and oxygenation reactions. |
| Route of elimination | 80% of the drug is excreted in the feces. |
| Half life | Not Available |
| Clearance | Not Available |
| Toxicity | Side effects include burning sensation, irritation, pruritus, erythema, and skin infections, at the application site. |