Alfacalcidol is a vitamin D analogue used for the management of hypocalcemia, secondary hyperparathyroidism, and osteodystrophy in patients with chronic renal failure, as well as some types of rickets and osteomalacia. Vitamin D is a secosteroid generated in the skin when 7-dehydrocholesterol located there interacts with ultraviolet irradiation - like that commonly found in sunlight. Vitamin D3 produced in the skin undergoes hydroxylation in the liver using the enzyme vitamin D 25-hydroxylase to form 25-hydroxyvitamin D3 (calcidiol). The second hydroxylation happens in the kidneys using the enzyme 25-hydroxy vitamin D 1α-hydroxylase to give 1, 25-dihydroxyvitamin D3 (calcitriol). Calcitriol interacts with vitamin D receptors in the small intestine to enhance the efficiency of intestinal calcium and phosphorous absorption from about 10-15% to 30-40% and 60% increased to 80%, respectively. Furthermore, calcitriol binds with vitamin D receptors in osteoblasts to stimulate a receptor activator of nuclear factor kB ligand (or RANKL) which subsequently interacts with receptor activator of nuclear factor kB (NFkB) on immature preosteoclasts, causing them to become mature bone-resorbing osteoclasts. Such mature osteoclasts ultimately function in removing calcium and phosphorus from bone to maintain blood calcium and phosphorus levels. Moreover, calcitriol also stimulates calcium reabsorption from the glomerular filtrate in the kidneys. Calcitrol is also involved in parathyroid hormone regulation, by lowering parathyroid hormone secretion. In conditions like chronic renal failure, renal bone disease, hypoparathyroidism, and vitamin D dependent rickets, the kidneys' capacity for 1α-hydroxylation is impaired, leading to reduced production of endogenous 1,25-dihydroxyvitamin D and aberrated mineral metabolism. Alfacalcidol is rapidly converted in the liver to 1,25-dihydroxyvitamin D and works to restore the functions and activities of endogenous 1,25-dihydroxyvitamin D.

Alfacalcidol Pathway References