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 absor ption of [H-3]1,24(OH)(2)D-3 (1,24-dihydroxyvitamin D-3; tacalcitol) b y 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 sk in at the application site 1 h after topical treatment showed a high c oncentration of radiolabel in the stratum corneum, the epidermis and a round the hair follicles, Radiolabel was also seen in the epidermis an d hair follicle areas 8 h and 24 h after application, The radiolabel w as distributed to a minor extent to the subcutaneous fat layer, Microa utoradiography showed two routes of purcutaneous absorption of 1,24(OH )(2)D-3: through the stratum corneum and epidermis into the microvesse ls, and through hair follicle areas into the bloodstream, After topica l application of an ointment containing 4 mu g/g or 40 mu g/g [H-3]1,2 4(OH)(2)D-3 to the shaved neck skin of rats, the absorption rate, esti mated by excretion in the urine and faeces, was about 30% of the total applied radioactivity, The main excretion route after topical applica tion was in the faeces, Furthermore, 1,24(OH)(2)D-3 added to human adu lt keratinocytes was not metabolized into other compounds, and only th e unchanged compound was detected, These findings strongly suggest tha t 1,24(OH)(2)D-3 distributed into the epidermis acts on epidermal kera tinocytes. Topical application of 1,24(OH)(2)D-3 appears to be a possi ble approach to the treatment of psoriasis and other skin diseases thr ough its action on the 1,25(OH)(2)D-3 receptor, which reportedly plays a very important role in the regulation of proliferation and differen tiation of keratinocytes.