Chemical Properties
White Crystalline Powder
Originator
Rocaltrol,Roche,US,1978
Definition
ChEBI: A hydroxycalciol that is calcidiol in which the pro-S hydrogen of calcidiol is replaced by a hydroxy group. It is the active form of vitamin D3, produced fom calciol via hydoxylation in the li
er to form calcidiol, which is subsequently oxidised in the kidney to give calcitriol.
Manufacturing Process
1α,25-Dihydroxyprecholecalciferol: A solution of 1α,25-
diacetoxyprecholecalciferol (0.712 g, 1.42 mmols), potassium hydroxide (2.0
g, 35.6 mmols) and methanol (40 ml) was stirred at room temperature under
argon for 30 hours. The reaction mixture was concentrated under reduced
pressure. Water (50 ml) was added to the residue and the mixture was
extracted with methylene chloride (3 x 100 ml). The combined organic
extracts were washed with saturated sodium chloride solution (3 x 50 ml),
dried over anhydrous sodium sulfate, filtered and evaporated under reduced
pressure to give 0.619 g of 1alpha,25-dihydroxyprecholecalciferol as a thick
oil.
1α,25-Dihydroxycholecalciferol: A solution of 1α,25-dihydroxyprecholecalciferol
[0.619 g in dioxane (30 ml)] was heated under reflux for 30 minutes under an
atmosphere of argon. The reaction mixture was concentrated under reduced pressure and the residue was purified with a Waters Associates liquid
chromatograph model 202 using a 8 foot * 3/8 inch Porasil A column and a
5:1 mixture of ethyl acetate-n-hexane as the eluent to give 0.474 g (80%
yield based on 1α,25-diacetoxyprecholecalciferol) of pure 1α,25-
dihydroxycholecalciferol. Recrystallization from methyl formate afforded 0.340
g of 1α,25-dihydroxcholecalciferol as colorless crystals, MP 113°-114°C.
Brand name
Calcijex (Abbott); Rocaltrol (Roche.
Therapeutic Function
Calcium regulator
General Description
1α,25-Dihydroxyvitamin D3, also referred as calcitriol, is a calcitrophic hormone. It is the most biologically active metabolite of vitamin D produced in proximal tubular cells in the kidney.
Biological Activity
Active metabolite of vitamin D 3 that activates the vitamin D receptor (VDR). Displays calcemic actions; stimulates intestinal and renal Ca 2+ absorption and regulates bone Ca 2+ turnover. Exhibits antitumor activity; inhibits in vivo and in vitro cell proliferation in a wide range of cells including breast, prostate, colon, skin and brain carcinomas and myeloid leukemia cells.
Biochem/physiol Actions
Biologically active form of vitamin D3 in calcium absorption and deposition. 1α,25-Dihydroxyvitamin D3 has widespread effects on cellular differentiation and proliferation, and can modulate immune responsiveness, and central nervous system function. Recent studies suggest that 1α,25-dihydroxyvitamin D3 acts as a chemopreventive agent against several malignancies including cancers of the prostate and colon and shows synergy with other anticancer compounds.
Clinical Use
Vitamin D analogue:
Promotes intestinal calcium absorption
Suppresses PTH production and release
Veterinary Drugs and Treatments
Calcitriol may be potentially beneficial in the adjunctive treatment
of chronic renal
disease in dogs and cats but its use is somewhat
controversial, particularly the decision on how soon in the course
of chronic renal insufficiency it should employed. It may also be of
benefit in treating some types of dermatopathies (primary idiopathic
seborrhea).
Drug interactions
Potentially hazardous interactions with other drugs
Antiepileptics: the effects of vitamin D may
be reduced in patients taking barbiturates or
anticonvulsants.
Diuretics: increased risk of hypercalcaemia with
thiazides.
Sevelamer: absorption may be impaired by sevelamer
Metabolism
During transport in the blood at physiological
concentrations, calcitriol is mostly bound to a specific
vitamin D binding protein (DBP), but also, to a lesser
degree, to lipoproteins and albumin. At higher blood
calcitriol concentrations, DBP appears to become
saturated, and increased binding to lipoproteins and
albumin occurs.
Calcitriol is inactivated in both the kidney and
the intestine, through the formation of a number
of intermediates including the formation of the
1,24,25-trihydroxy derivatives. It is excreted in the bile
and faeces and is subject to enterohepatic circulation.
storage
-20°C, protect from light, stored under nitrogen,unstable in solution, ready to use.
