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Identification
Name Calcitriol
Accession Number DB00136 (APRD00246, NUTR00003)
Type small molecule
Groups approved, nutraceutical
Description

Calcitriol or 1,25-dihydroxycholecalciferol (abbreviated 1,25-(OH)2-D3) is the active form of vitamin D found in the body (vitamin D3). Calcitriol is marketed under various trade names including Rocaltrol (Roche), Calcijex (Abbott) and Decostriol (Mibe, Jesalis). It is produced in the kidneys via 25-hydroxyvitamin D-1 α-hydroxylase by conversion from 25-hydroxycholecalciferol (calcidiol). This is stimulated by a decrease in serum calcium, phosphate (PO43−) and parathyroid hormone (PTH) levels. It regulates calcium levels by increasing the absorption of calcium and phosphate from the gastrointestinal tract, increasing calcium and phosphate reabsorption in the kidneys and inhibiting the release of PTH. Calcitriol is also commonly used as a medication in the treatment of hypocalcemia and osteoporosis.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • 1,25-(OH)2D3
  • 1,25-dihydroxycholecalciferol
Brand names
  • Calcijex (Abbott)
  • Calcitriol Oral Solution (Roxane)
  • Decostriol (Mibe Jena (Germany), Jesalis (Hong Kong, Thailand))
  • Rocaltrol (Roche)
Brand name mixtures Not Available
Categories
  • Essential Vitamin
  • Antihypocalcemic Agents
  • Antihypoparathyroid Agents
  • Vitamins (Vitamin D)
  • Bone Density Conservation Agents
  • Calcium Channel Agonists
  • Vitamins
CAS number 32222-06-3
Weight Average: 416.6365
Monoisotopic: 416.329045274
Chemical Formula C27H44O3
InChI Key InChIKey=GMRQFYUYWCNGIN-ZVUFCXRFSA-N
InChI
InChI=1S/C27H44O3/c1-18(8-6-14-26(3,4)30)23-12-13-24-20(9-7-15-27(23,24)5)10-11-21-16-22(28)17-25(29)19(21)2/h10-11,18,22-25,28-30H,2,6-9,12-17H2,1,3-5H3/t18-,22-,23-,24+,25+,27-/m1/s1
Plain Text
IUPAC Name
(1R,3S)-5-{2-[(1R,3aS,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-octahydro-1H-inden-4-ylidene]ethylidene}-4-methylidenecyclohexane-1,3-diol
SMILES
[H][C@@]1(CC[C@@]2([H])C(CCC[C@]12C)=CC=C1C[C@@H](O)C[C@H](O)C1=C)[C@H](C)CCCC(C)(C)O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Alcohols and Polyols
  • Isoprenes
Substructures
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Alcohols and Polyols
  • Isoprenes
Pharmacology
Indication Used to treat vitamin D deficiency or insufficiency, refractory rickets (vitamin D resistant rickets), familial hypophosphatemia and hypoparathyroidism, and in the management of hypocalcemia and renal osteodystrophy in patients with chronic renal failure undergoing dialysis. Also used in conjunction with calcium in the management and prevention of primary or corticosteroid-induced osteoporosis.
Pharmacodynamics Calcitriol, a pharmaceutical form of vitamin D, has anti-osteoporotic, immunomodulatory, anticarcinogenic, antipsoriatic, antioxidant, and mood-modulatory activities. Calcitriol has been found to be effective in the treatment of psoriasis when applied topically. Calcitriol has been found to induce differentiation and/or inhibit cell proliferation in a number of malignant cell lines including human prostate cancer cells. Vitamin D deficiency has long been suspected to increase the susceptibility to tuberculosis. The active form of calcitriol, 1,25-(OH)2-D3, has been found to enhance the ability of mononuclear phagocytes to suppress the intracellular growth of Mycobacterium tuberculosis. 1,25-(OH)2-D3 has demonstrated beneficial effects in animal models of such autoimmune diseases as rheumatoid arthritis. It has also been found to induce monocyte differentiation and to inhibit lymphocyte proliferation and production of cytokines, including interleukin IL-1 and IL-2, as well as to suppress immunoglobulin secretion by B lymphocytes. Vitamin D appears to demonstrate both immune-enhancing and immunosuppressive effects.
Mechanism of action The mechanism of action of calcitriol in the treatment of psoriasis is accounted for by their antiproliferative activity for keratinocytes and their stimulation of epidermal cell differentiation. The anticarcinogenic activity of the active form of Calcitriol appears to be correlated with cellular vitamin D receptor (VDR) levels. Vitamin D receptors belong to the superfamily of steroid-hormone zinc-finger receptors. VDRs selectively bind 1,25-(OH)2-D3 and retinoic acid X receptor (RXR) to form a heterodimeric complex that interacts with specific DNA sequences known as vitamin D-responsive elements. VDRs are ligand-activated transcription factors. The receptors activate or repress the transcription of target genes upon binding their respective ligands. It is thought that the anticarcinogenic effect of Calcitriol is mediated via VDRs in cancer cells. The immunomodulatory activity of calcitriol is thought to be mediated by vitamin D receptors (VDRs) which are expressed constitutively in monocytes but induced upon activation of T and B lymphocytes. 1,25-(OH)2-D3 has also been found to enhance the activity of some vitamin D-receptor positive immune cells and to enhance the sensitivity of certain target cells to various cytokines secreted by immune cells.
Absorption Rapidly absorbed from the intestine.
Volume of distribution Not Available
Protein binding 99.9%
Metabolism

The first pathway involves 24-hydroxylase activity in the kidney; this enzyme is also present in many target tissues which possess the vitamin D receptor such as the intestine. The end product of this pathway is a side chain shortened metabolite, calcitroic acid. The second pathway involves the conversion of calcitriol via the stepwise hydroxylation of carbon-26 and carbon-23, and cyclization to yield ultimately 1a,25R(OH)2-26,23S-lactone D3. The lactone appears to be the major metabolite circulating in humans.
Route of elimination Enterohepatic recycling and biliary excretion of calcitriol occur. The metabolites of calcitriol are excreted primarily in feces. Cumulative excretion of radioactivity on the sixth day following intravenous administration of radiolabeled calcitriol averaged 16% in urine and 49% in feces.
Half life 5-8 hours
Clearance
  • 15.3 mL/hr/kg [pediatric patients (age range: 1.8 to 16 years) undergoing peritoneal dialysis receiving dose of 10.2 ng/kg (SD 5.5 ng/kg) for 2 months]
Toxicity LD50 (oral, rat) = 620 μg/kg; LD50 (intraperitoneal, rat) > 5 mg/kg; Overdose evident in elevated blood calcium levels causing symptoms of anorexia, nausea and vomiting, polyuria, polydipsia, weakness, pruritus, and nervousness, potentially with irreversible calcification of soft tissue in the kidney and liver.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Roxane laboratories inc
  • Teva pharmaceuticals usa inc
  • Validus pharmaceuticals llc
  • Abbott laboratories hosp products div
  • Akorn inc
  • App pharmaceuticals llc
  • Fresenius medical care north america
  • Genix therapeutics inc
  • Hospira inc
  • Luitpold pharmaceuticals inc
  • Lyne laboratories inc
  • Teva parenteral medicines inc
  • Galderma laboratories lp
Packagers
Dosage forms
Form Route Strength
Capsule Oral 0.25 mcg
Capsule Oral 0.5 mcg
Solution Intravenous 1 mcg/ml
Solution Intravenous 2 mcg/ml
Solution Oral 1 mcg/ml
Prices
Unit description Cost Unit
Calcijex 2 mcg/ml 19.38 USD ml
Calcijex 1 mcg/ml ampul 14.7 USD ml
Calcijex 1 mcg/ml 10.68 USD ml
Calcitriol 1 mcg/ml ampul 6.0 USD ml
Vectical 3 mcg/g ointment 4.68 USD g
Rocaltrol 0.5 mcg capsule 2.02 USD capsule
Calcitriol 0.5 mcg capsule 1.97 USD capsule
Rocaltrol 0.25 mcg capsule 1.46 USD capsule
Calcitriol 0.25 mcg capsule 1.45 USD capsule
Patents
Country Patent Number Approved Expires
United States 6051567 2000-02-02 2020-02-02
Properties
State solid
Melting point 113 oC
Experimental Properties
Property Value Source
water solubility Insoluble PhysProp
logP 5 PhysProp
Predicted Properties
Property Value Source
water solubility 6.67e-03 g/l ALOGPS
logP 5.51 ALOGPS
logP 4.35 ChemAxon Molconvert
logS -4.80 ALOGPS
pKa 15.29 ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 3 ChemAxon Molconvert
polar surface area 60.69 ChemAxon Molconvert
rotatable bond count 6 ChemAxon Molconvert
refractivity 126.53 ChemAxon Molconvert
polarizability 51.43 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00129 Link_out
KEGG Compound C01673 Link_out
PubChem Compound 5283740 Link_out
PubChem Substance 46508162 Link_out
ChemSpider 118219 Link_out
ChEBI 17823 Link_out
ChEMBL 17823 Link_out
Therapeutic Targets Database DAP000289 Link_out
PharmGKB PA448717 Link_out
Drug Product Database 2245686 Link_out
RxList http://www.rxlist.com/cgi/generic2/calcitri.htm Link_out
Drugs.com http://www.drugs.com/cdi/calcitriol.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/vit_0265.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Calcitriol Link_out
ATC Codes
  • A11CC04
  • D05AX03
AHFS Codes
  • 88:16.00
PDB Entries Not Available
FDA label show (39.2 KB)
MSDS show (74.7 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Vitamin D3 receptor

Pharmacological action: yes
Actions: antagonist

Nuclear hormone receptor. VDR mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes

Organism class: human
UniProt ID: P11473 Link_out
Gene: VDR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Reinhart GA: Vitamin D analogs: novel therapeutic agents for cardiovascular disease? Curr Opin Investig Drugs. 2004 Sep;5(9):947-51. Pubmed
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Enzymes

1. Cytochrome P450 24A1, mitochondrial

Actions: substrate, inducer

Has a role in maintaining calcium homeostasis. Catalyzes the NADPH-dependent 24-hydroxylation of 25-hydroxyvitamin D(3) in the presence of adrenodoxin and NADPH-adrenodoxin reductase

UniProt ID: Q07973 Link_out
Gene: CYP24A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Schuster I: Cytochromes P450 are essential players in the vitamin D signaling system. Biochim Biophys Acta. 2010 Jul 7. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A4

Actions: substrate, inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Xu Y, Hashizume T, Shuhart MC, Davis CL, Nelson WL, Sakaki T, Kalhorn TF, Watkins PB, Schuetz EG, Thummel KE: Intestinal and hepatic CYP3A4 catalyze hydroxylation of 1alpha,25-dihydroxyvitamin D(3): implications for drug-induced osteomalacia. Mol Pharmacol. 2006 Jan;69(1):56-65. Epub 2005 Oct 5. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:36

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.