Cholecalciferol (Vitamin D3) – pharmacological properties, therapeutic utility and potential new fields of clinical application

personАвтори: G. Momekov, P. Peikov, Y. Voynikov


Vitamin D is a secosteroid produced in the skin from 7-dehydrocholesterol under the influence of ultraviolet irradiation. Vitamin D is also found in certain foods and is used to supplement dairy products. Both the natural form (vitamin D3, cholecalciferol) and the plant-derived form (vitamin D2, ergocalciferol) are present in the diet. These forms differ in that ergocalciferol contains a double bond (C22–23) and an additional methyl group in the side chain. Ergocalciferol is less potent and has some pharmacokinetic disadvantages that have unambiguously outlined cholecalciferol as the optimal agent for vitamin D supplementation. Vitamin D is a prohormone that serves as a precursor to a number of biologically active metabolites. It is first hydroxylated in the liver to form 25-hydroxyvitamin D (25(OH)D). This metabolite is further converted in the kidney to a number of other forms, the best-studied of which are 1,25-dihydroxyvitamin D (1,25(OH)2D) and 24,25-dihydroxyvitamin D (24,25(OH)2D). Of the natural metabolites, only vitamin D and 1,25(OH)2D (as calcitriol) are available for clinical use. Moreover, a number of analogs of 1,25(OH)2D are being synthesized to extend the usefulness of this metabolite to a variety of nonclassic conditions. Calcipotriol, for instance, is being used to treat psoriasis, a hyperproliferative skin disorder. Doxercalciferol and paricalcitol have recently been approved for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease. Other analogs are being investigated for the treatment of various disease states. The regulation of vitamin D metabolism is complex, involving calcium, phosphate, and a variety of hormones, the most important of which is PTH, which stimulates the production of 1,25(OH)2D by the kidney. Despite the specific advantages of analogs/metabolites, cholecalciferol has been well appreciated as effective in diverse conditions due to primary or secondary vitamin D deficiency and moreover has superior safety profile and is less expensive. The present paper is focused on a concise outline of the clinically-validated therapeutic applications of cholecalciferol with a prospectus for further therapeutic utilities, based on its pleiotropic effects beyond the calcium homeostasis and bone health.

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