Calcidiol Other names: Calcifediol Calcifidiol

Vitamin D has two main forms: D₂ (ergocalciferol) and D₃ (cholecalciferol). Vitamin D₃ is synthesized in the skin by exposure to sunlight (ultraviolet radiation) and is obtained from the diet. Vitamin D₃ must undergo a two-step metabolic process to be active; the first step occurs in the microsomal fraction of the liver where Vitamin D is hydroxylated at position 25 (25-hydroxycholecalciferol or calcifediol); the second step takes place in the kidney where 1,25-dihydroxycholecalciferol or calcitriol is formed due to the activity of enzyme 25-hydroxycholecalciferol 1-hydroxylase; conversion to 1,25-dihydroxycholecalciferol is regulated by its own concentration, by parathyroid hormone (PTH) and by serum calcium and phosphate concentration. Other metabolites with unknown function exist. 1,25-dihydroxycholecalciferol is transported from the kidney to target tissues (intestine, bone and possibly kidney and parathyroid gland) by binding to specific plasma proteins.

Pharmacodynamic effects

Vitamin D increases absorption of calcium and phosphorus in the intestine and improves normal bone formation and mineralization and acts on three levels:

Intestine: Vitamin D enhances absorption of calcium and phosphorus in the small intestine.

Bone: calcitriol enhances bone formation by increasing levels of calcium and phosphate and stimulates action of osteoblasts.

Kidney: calcitriol enhances tubular reabsorption of calcium.

Parathyroid glands: vitamin D inhibits the secretion of parathyroid hormone.

Absorption

Calcifediol or 25-hydroxycholecalciferol, as an analogue to vitamin D, is well absorbed in the intestine if fat absorption is normal, through chylomicrons, mainly in the middle portions of the small intestine; approximately 75-80% is absorbed through this process.

Distribution

Calcifediol is the major circulating form of vitamin D. Serum concentrations of 25-OH-cholecalciferol reflect the vitamin D stored in the body, usually from 25 to 40 ng/ml (62.5 to 100 nmol/l) in healthy subjects. Following oral administration of calcifediol, the maximum serum concentration is reached after 4 hours approximately. Its half-life is around 18 to 21 days and storage in adipose tissue is less significant than vitamin D, due to its lower lipid solubility. Calcifediol is stored in adipose tissue and muscle for prolonged periods.

Elimination

Calcifediol is primarily excreted in the bile.

High doses of vitamin D (4 to 15 times the recommended dose in humans) have proved to be teratogenic in animals, but there are few studies in humans. Vitamin D can cause hypercalcemia in pregnant women, which could lead to a syndrome of supravalvar aortic stenosis, retinopathy and mental retardation in infants and newborn.