COMPARISON OF CALCIPOTRIOL WITH SELECTED METABOLITES AND ANALOGS OF VITAMIN-D(3) - EFFECTS ON CELL-GROWTH REGULATION INVITRO AND CALCIUM-METABOLISM INVIVO

Calcipotriol is a novel vitamin D3 analogue developed for topical treatment of psoriasis. Calcipotriol is believed to act via regulation of cell proliferation and differentiation. In this respect calcipotriol il as potent as 1alpha,25(OH)2D3, the physiologically active form of vitamin D3, but its calcaemic activity in vivo is 100 to 200 times lower. In the present investigation, the effects of calcipotriol on cell growth regulation in vitro and on calcium metabolism in vivo were compared to those exerted by a number of metabolites and analogues of vitamin D3. Besides 1alpha,25(OH)2D3, these included the two physiologically occurring metabolites 25(OH)D3 and 24,25(OH)2D3, and the two synthetic analogues 1alpha((OH)D3 and 1alpha,24(OH)2D3. 25(OH)D3 and 24,25(OH)2D3 were shown to be inactive both in vitro and in vivo. 1alpha(OH)D3 was found to have a low biological activity in vitro, but was highly calcaemic in vivo after biotransformation to 1alpha,25(OH)2D3. Calcipotriol, 1alpha,24(OH)2D3 and 1alpha,25(OH)2D3 Were all three potent regulators of cell proliferation and differentiation in vitro. In vivo, only calcipotriol showed a greatly reduced calcaemic activity after both oral and intravenous administration. It is concluded that calcipotriol, with a reduced risk of inducing calcaemic side-effects upon absorption from the skin, possesses a favourable therapeutic profile for topical treatment of hyperproliferative diseases.