The ability of methotrexate sodium to penetrate skin in vivo has been studied in hairless mice and psoriatic patients. When topically applied, methotrexate was rapidly absorbed through hairless mouse skin, but not through human skin. In mice, topically applied methotrexate was detected in the plasma, skin, and liver in amounts comparable to those obtained after intraperitoneal injection. Following topical application in psoriatic patients, methotrexate could be detected in neither plasma nor skin. Repeated topical application and intralesional injections of methotrexate were clinically ineffective in 17 out of 18 psoriatic patients so treated. Possible reasons for the ineffectiveness of local application of methotrexate in psoriasis are discussed.
Stewart WD, Wallace SM, Runikis JO. Absorption and Local Action of Methotrexate in Human and Mouse Skin. Arch Dermatol. 1972;106(3):357-361. doi:10.1001/archderm.1972.01620120045009