PERCUTANEOUS-ABSORPTION OF METHOTREXATE - EFFECT ON EPIDERMAL DNA-SYNTHESIS IN HAIRLESS MICE

[摘要] One of the presumed reasons for the lack of clinical activity of topical methotrexate in psoriasis is insufficient percutaneous penetration necessary to inhibit epidermal DNA synthesis. A vehicle to optimize penetration of methotrexate in vitro was selected and the effects of this topical formulation on epidermal DNA synthesis in vivo in hairless mouse skin was determined. Increased penetration of methotrexate was obtained in human skin in vitro with Vehicle N compared to water and n-decylmethylsulfoxide vehicles. Repeated topical application of this methotrexate/Vehicle N preparation produced marked epidermal atrophy in treated sites in both normal and hyperproliferative essential fatty acid deficient hairless mouse skin, without similar effects at a distant skin site. Local inhibition of epidermal DNA synthesis was obtained without systemic effects at a distant site. Methotrexate in Vehicle N may produce a direct effect on epidermis which may be useful for the topical therapy of psoriasis.