Pimecrolimus identifies a common genomic anti-inflammatory profile, is clinically highly effective in psoriasis and is well tolerated

JOURNAL OF INVESTIGATIVE DERMATOLOGY

卷:119

Article

Rappersberger, K ; Komar, M ; Ebelin, ME ; Scott, G ; Burtin, P ; Greig, G ; Kehren, J ; Chibout, SD ; Cordier, A ; Holter, W ; Richter, L ; Oberbauer, R ; Stuetz, A ; Wolff, K

关键词: ascomycin;    pharmacogenomics;    pharmacokinetics;    pimecrolimus;    psoriasis;   

DOI  :  10.1046/j.1523-1747.2002.00694.x

来源: Elsevier

【 摘 要 】

The ascomycin macrolactam pimecrolimus is a novel inflammatory cytokine release inhibitor that so far has not been administered systemically to humans. In this phase I/II randomized double-blind, placebo-controlled, multiple rising dose proof of concept study psoriasis patients were treated with oral pimecrolimus or placebo. Gene profiling identified a common genomic profile with a downregulation of genes associated with inflammation but no changes in gene expression linked to drug-related side-effects. A steady state of pimecrolimus was reached after 5-10 d, C-max, and area under the curve (0-24) was 54.5 ng per ml and 589.9 ng h per ml, respectively, at steady state at the highest dose. There was clear clinical efficacy in patients receiving 20 mg pimecrolimus twice daily and 30 mg twice daily with a reduction of Psoriasis Area and Severity Index by 60% and 75%, respectively. Histopathologically and immunopathologically there was a reversion of the psoriatic phenotype towards normal. There were no notable clinical, laboratory, kidney function, or immunologic side-effects. We conclude that pimecrolimus taken orally is highly effective in a concentration-dependent manner in patients with psoriasis and on a short-term basis it is well tolerated and this is confirmed by its pharmacogenomic profile. The latter also indicates that pimecrolimus should be equally effective in other inflammatory skin diseases.

【 授权许可】

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