Calcifediol (25-Hydroxyvitamin D3 or 25-hydroxycholecalciferol) is a biologically active vitamin D3 metabolite. It is concluded that the liver is the major if not the only physiologic site of hydroxylation of vitamin D3 into calcifediol. Calcifediol is a prohormone of the active form of vitamin D3, calcitriol (1,25-dihydroxyvitamin D3). Calcifediol is converted to calcitriol by cytochrome P450 27B1 (CYP27B1), also called 1-alpha hydroxylase, primarily in the kidney. Calcitriol binds to the vitamin D receptor in target tissues and activates vitamin D responsive pathways that result in increased intestinal absorption of calcium and phosphorus and reduced parathyroid hormone synthesis. RAYALDEE (calcifediol) extended-release capsules is indicated for the treatment of secondary hyperparathyroidism in adult patients with stage 3 or 4 chronic kidney disease.

Trans-calcitriol or Calcitriol Impurity A, is the impurity of Calcitriol. Calcitriol is the hormonally active form of vitamin D, Calcitriol is the active metabolite of vitamin D3 that activates the vitamin D receptor (VDR). Calcitriol Impurity A is the physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (CALCIFEDIOL). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption.

Cholecalciferol (/ˌkoʊləkælˈsɪfərɒl/) (vitamin D3) is one of the five forms of vitamin D. Cholecalciferol is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, in mineralization of bone, and for the assimilation of Vitamin A. The classical manifestation of vitamin D deficiency is rickets, which is seen in children and results in bony deformities including bowed long bones. Most people meet at least some of their vitamin D needs through exposure to sunlight. Ultraviolet (UV) B radiation with a wavelength of 290–320 nanometers penetrates uncovered skin and converts cutaneous 7-dehydrocholesterol to previtamin D3, which in turn becomes vitamin D3. In supplements and fortified foods, vitamin D is available in two forms, D2 (ergocalciferol) and D3 (cholecalciferol) that differ chemically only in their side-chain structure. Vitamin D2 is manufactured by the UV irradiation of ergosterol in yeast, and vitamin D3 is manufactured by the irradiation of 7-dehydrocholesterol from lanolin and the chemical conversion of cholesterol. The two forms have traditionally been regarded as equivalent based on their ability to cure rickets and, indeed, most steps involved in the metabolism and actions of vitamin D2 and vitamin D3 are identical. Both forms (as well as vitamin D in foods and from cutaneous synthesis) effectively raise serum 25(OH) D levels. Firm conclusions about any different effects of these two forms of vitamin D cannot be drawn. However, it appears that at nutritional doses, vitamins D2 and D3 are equivalent, but at high doses, vitamin D2 is less potent. The American Academy of Pediatrics (AAP) recommends that exclusively and partially breastfed infants receive supplements of 400 IU/day of vitamin D shortly after birth and continue to receive these supplements until they are weaned and consume ≥1,000 mL/day of vitamin D-fortified formula or whole milk. Cholecalciferol is used in diet supplementary to treat Vitamin D Deficiency. Cholecalciferol is inactive: it is converted to its active form by two hydroxylations: the first in the liver, the second in the kidney, to form calcitriol, whose action is mediated by the vitamin D receptor, a nuclear receptor which regulates the synthesis of hundreds of enzymes and is present in virtually every cell in the body. Calcitriol increases the serum calcium concentrations by increasing GI absorption of phosphorus and calcium, increasing osteoclastic resorption, and increasing distal renal tubular reabsorption of calcium. Calcitriol appears to promote intestinal absorption of calcium through binding to the vitamin D receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein.

24-Hydroxycalcidiol (24,25-dihydroxy vitamin D3) is a circulating metabolite of vitamin D3. 24,25(OH)2D3 functions by activation of Vitamin D receprtor and promotion of ostecalcin expression, but is less effective than other D3 metabolite, 1alpha,25(OH)2D3. There is conflicting evidence on efffect of 24-hydroxycalcidiol on bone metabolism. In several animal studies it was demonstrated that 24-hydroxycalcidiol was able to stimulate calcification of bone and restore the reduction in bone mineral apposition rate. However, no beneficial effect of 24R,25(OH)2D3 treatment of postmenapausal women on bone mineral density or bone loss and calcium metabolism were observed.

Pefcalcitol (previously known as M518101), an analog of vitamin D3 (VD3), is an antipsoriatic drug candidate that is designed to achieve much higher pharmacological effects, such as keratinocyte differentiation. This drug is a phosphodiesterase inhibitor and is being developed as a topical ointment formulation. Pefcalcitol was involved in phase III clinical trials in the USA and in Japan in subjects with plaque psoriasis and with palmoplantar keratoderma. In addition, it participated in phase II clinical trial for the warts treatment.

Becocalcidiol is a vitamin D analog participated in phase II clinical trials as a topical treatment for psoriasis. Therapy was safe and well tolerated, however further studies were discontinued.

Seocalcitol (EB 1089) is a vitamin D analog, and agonist of the vitamin D receptor. Antineoplastic activity of seocalcitol was tested in clinical trials against hepatocellular carcinoma, pancreatic, breast and colorectal cancer. Due to inconsistent results of clinical trials, development of seocalcitol was discontinued by Leo Pharma.