Calcitriol 32222-06-3

Nomenclature

Calcitriol usually refers specifically to 1,25-dihydroxycholecalciferol, but may also sometimes include 24,25-dihydroxycholecalciferol (when specified). Because cholecalciferol already has one alcohol group, only two are further specified in the nomenclature. Calcitriol is marketed under various trade names including Rocaltrol , Calcijex and Decostriol (Mibe, Jesalis).

Function

Calcitriol increases blood calcium levels ( [Ca²⁺] ) by promoting absorption of dietary calcium from the gastrointestinal tract and increasing renal tubular reabsorption of calcium thus reducing the loss of calcium in the urine. Calcitriol also stimulates release of calcium from bone by its action on the specific type of bone cells referred to as osteoclasts. Calcitriol acts in concert with parathyroid hormone (PTH) in all three of these roles. For instance, PTH also stimulates osteoclasts. However, the main effect of PTH is to increase the rate at which the kidneys excrete inorganic phosphate (P_i), the counterion of Ca²⁺. The resulting decrease in serum phosphate causes Ca₅(PO₄)₃OH to dissolve out of bone thus increasing serum calcium. PTH also stimulates the production of calcitriol (see below).

Biosynthesis and its regulation

Calcitriol is produced in the cells of the proximal tubule of the nephron in the kidneys by the action of 25-hydroxyvitamin D₃ 1-alpha-hydroxylase, a mitochondrial oxygenase and an enzyme which catalyzes the hydroxylation of 25-hydroxycholecalciferol (calcifediol). The activity of the enzyme is stimulated by PTH. The reaction is an important control point in Ca²⁺ homeostasis. *Treatment of hypocalcaemia – hypoparathyroidism, osteomalacia (adults), rickets (infants, children), renal osteodystrophy, chronic renal dialysis*Treatment of osteoporosis*Prevention of corticosteroid-induced osteoporosisCalcitriol is also sometimes used topically in the treatment of psoriasis, however the evidence to support its efficacy is not well established. The vitamin D analogue calcipotriol is more commonly used for psoriasis. Research on the noncalcemic actions of calcitriol and other VDR-ligand analogs and their possible therapeutic applications has been reviewed.

Adverse effects

The main adverse drug reaction associated with calcitriol therapy is hypercalcaemia – early symptoms include: nausea, vomiting, constipation, anorexia, apathy, headache, thirst, sweating, and/or polyuria). Compared to other vitamin D compounds in clinical use , calcitriol has a higher risk of inducing hypercalcaemia. However, such episodes may be shorter and easier to treat due to its relatively short half-life.