In vivo microautoradiography of [H-3]1,24(OH)(2)D-3 (tacalcitol) following topical application to normal rats and in vitro metabolism in human keratinocytes

This study was conducted to investigate the mechanism of topical absorption of [H-3]1,24(OH)(2)D-3 (1,24-dihydroxyvitamin D-3; tacalcitol) by applying an ointment containing 4 mu g/g [H-3]1,24(OH)(2)D-3 to the skin of rats using an occlusion method, Microautoradiography of the skin at the application site 1 h after topical treatment showed a high concentration of radiolabel in the stratum corneum, the epidermis and around the hair follicles, Radiolabel was also seen in the epidermis and hair follicle areas 8 h and 24 h after application, The radiolabel was distributed to a minor extent to the subcutaneous fat layer, Microautoradiography showed two routes of purcutaneous absorption of 1,24(OH)(2)D-3: through the stratum corneum and epidermis into the microvessels, and through hair follicle areas into the bloodstream, After topical application of an ointment containing 4 mu g/g or 40 mu g/g [H-3]1,24(OH)(2)D-3 to the shaved neck skin of rats, the absorption rate, estimated by excretion in the urine and faeces, was about 30% of the total applied radioactivity, The main excretion route after topical application was in the faeces, Furthermore, 1,24(OH)(2)D-3 added to human adult keratinocytes was not metabolized into other compounds, and only the unchanged compound was detected, These findings strongly suggest that 1,24(OH)(2)D-3 distributed into the epidermis acts on epidermal keratinocytes. Topical application of 1,24(OH)(2)D-3 appears to be a possible approach to the treatment of psoriasis and other skin diseases through its action on the 1,25(OH)(2)D-3 receptor, which reportedly plays a very important role in the regulation of proliferation and differentiation of keratinocytes.