ActiveD Calcitriol 0.25 mcg Tablets

Description
Calcitriol is a synthetic vitamin D analog which is active in the regulation of the absorption of calcium from the gastrointestinal tract and its utilization in the body. Calcitriol is a white, crystalline compound which occurs naturally in humans. It has a calculated molecular weight of 416.65 and is soluble in organic solvents but relatively insoluble in water.
Composition
ActiveD is available as soft gelatin capsules containing 0.25 micrograms of Calcitriol.
PharmacologyPharmacodynamics
Calcitriol is the most important active metabolite of Vitamin D₃. It is normally formed in the kidney from its precursor 25-hydroxycholecalciferol (25-HCC). Physiological daily production is normally 0.5 – 1.0µg and is somewhat higher during periods of increased bone synthesis (e.g., growth or pregnancy). The natural supply of Vitamin D in humans depend mainly on exposure to ultraviolet rays of the sun for conversion of 7-dehydrocholesterol in the skin to Vitamin D₃ (cholecalciferol). Vitamin D₃ must be metabolically activated in the liver and the kidney before it is fully active as a regulator of calcium and phosphorus metabolism at target tissues. The initial transformation of Vitamin D₃ is catalysed by a Vitamin D₃-25-hydroxylase enzyme (25-OHase) present in the liver and the product of this reaction is 25-hydroxyvitamin D₃ [25-(OH) D₃]. Hydroxylation of 25-(OH) D₃ occurs in the mitochondria of kidney tissue, activated by the renal 25-hydroxyvitamin D₃-1 alpha-hydroxylase (alpha-OHase), to produce 1,25-(OH)₂ D₃ (Calcitriol), the active form of Vitamin D₃.
Calcitriol binds to an intracellular receptor, a member of the steroid receptor superfamily. The calcitriol receptor complex interacts with specific DNA sequences that regulate transcription and protein synthesis in a variety of cells including osteoblasts, mucosal cells of the intestine, renal tubular cells and parathyroid cells. The changes in protein synthesis induced in these cells by Calcitriol are responsible for its profound physiological effects. A Vitamin D-resistant state exists in uremic patients because of the failure of the kidney to convert precursors to the active compound. The uremic state may also inhibit the binding of the Calcitriol receptor to its specific DNA responsive elements. The key role of Calcitriol in the regulation of bone and calcium homeostasis, which includes stimulating effects on osteoblastic activity in the skeleton, provides a sound pharmacological basis for its therapeutic effects in osteoporosis. The treatment of established osteoporosis with Calcitriol is associated with an increase in bone density and a reduction in new vertebral fractures. Established osteoporosis is defined as the finding of bone mineral density measurements of 2 or more standard deviations below the gender specific peak bone mass; or the presence or history of osteoporotic fracture. Calcitriol also reduces bone loss associated with corticosteroid therapy.
In patients with marked renal impairment, synthesis of endogenous Calcitriol is correspondingly limited or may even cease altogether. This deficiency plays a key role in the development of renal osteodystrophy.