Comparison of calcipotriol with selected metabolites and analogues of vitamin D3: effects on cell growth regulation in vitro and calcium metabolism in vivo.
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 is as potent as 1 alpha, 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 1 alpha, 25(OH)2D3, these included the two physiologically occurring metabolites 25(OH)D3 and 24,25(OH)2D3, and the two synthetic analogues 1 alpha (OH)D3 and 1 alpha, 24(OH)2D3. 25(OH)D3 and 24,25(OH)2D3 were shown to be inactive both in vitro and in vivo. 1 alpha (OH)D3 was found to have a low biological activity in vitro, but was highly calcaemic in vivo after biotransformation to 1 alpha, 25(OH)2D3. Calcipotriol, 1 alpha, 24(OH)2D3 and 1 alpha, 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.
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Department of Biology and Toxicology, Leo Pharmaceutical Products 55, Ballerup, Denmark.
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002762:Cholecalciferol / Q000378:metabolism / Q000494:pharmacology*; D003879:Dermatologic Agents / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051381:Rats; D011917:Rats, Inbred Lew; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism; D014407:Tumor Cells, Cultured
D003879:Dermatologic Agents; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; C055085:calcipotriene; D002762:Cholecalciferol; D002117:Calcitriol; D002118:Calcium