Calcitriol

Calcitriol

Clinical data
Pronunciation	US /ˌkælsᵻˈtraɪ.ɒl/; UK /kælˈsɪtri.ɒl/
Trade names	Rocaltrol, Calcijex, Decostriol
MedlinePlus	a682335
Pregnancy category	AU: B3 US: C (Risk not ruled out)
Routes of administration	Oral, IV, topical
ATC code	A11CC04 (WHO) D05AX03 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Protein binding	99.9%
Metabolism	Renal
Biological half-life	5–8 hours (adults), 27 hours (children)
Excretion	Faeces (50%), urine (16%)
Identifiers
IUPAC name (1R,3S)-5-[2-[(1R,3aR,7aS)-1-[(2R)-6-hydroxy-6-methyl-heptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H- inden-4-ylidene]ethylidene]-4-methylidene-cyclohexane-1,3-diol
CAS Number	32222-06-3 Y
PubChem (CID)	5280453
IUPHAR/BPS	2779
DrugBank	DB00136 Y
ChemSpider	4444108 Y
UNII	FXC9231JVH Y
ChEBI	CHEBI:17823 Y
ChEMBL	CHEMBL846 Y
ECHA InfoCard	100.046.315
Chemical and physical data
Formula	C27H44O3
Molar mass	416.64 g/mol
3D model (Jmol)	Interactive image
SMILES C[C@H](CCCC(C)(C)O)[C@H]1CC[C@@H]\2[C@@]1(CCC/C2=C\C=C/3\C[C@H](C[C@@H](C3=C)O)O)C
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/b20-10+,21-11-/t18-,22-,23-,24+,25+,27-/m1/s1 Y Key:GMRQFYUYWCNGIN-NKMMMXOESA-N Y

Calcitriol (INN), also called 1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin D₃, is the hormonally active metabolite of vitamin D with three hydroxyl groups (abbreviated 1,25-(OH)₂D₃ or simply 1,25(OH)₂D), It was first identified by Michael F. Holick in work published in 1971. Calcitriol increases the level of calcium (Ca²⁺) in the blood by increasing the uptake of calcium from the gut into the blood, and possibly increasing the release of calcium into the blood from bone.

Calcitriol usually refers specifically to 1,25-dihydroxycholecalciferol. Because cholecalciferol already has one hydroxyl group, only two are further specified in the nomenclature.

Calcitriol is marketed under various trade names including Rocaltrol (Roche), Calcijex (Abbott), Decostriol (Mibe, Jesalis), Biowoz (Solmarc) and Vectical (Galderma), Rolsical (Sun Pharma).

Calcitriol increases blood calcium levels ([Ca²⁺]) by:

Calcitriol acts in concert with parathyroid hormone (PTH) in all three of these roles. For instance, PTH also indirectly 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 hydroxyapatite (Ca₅(PO₄)₃OH) to dissolve out of bone thus increasing serum calcium. PTH also stimulates the production of calcitriol (see below).

Many of the effects of calcitriol are mediated by its interaction with the calcitriol receptor, also called the vitamin D receptor or VDR. For instance, the unbound inactive form of the calcitriol receptor in intestinal epithelial cells resides in the cytoplasm. When calcitriol binds to the receptor, the ligand-receptor complex translocates to the cell nucleus, where it acts as a transcription factor promoting the expression of a gene encoding a calcium binding protein. The levels of the calcium binding protein increase enabling the cells to actively transport more calcium (Ca²⁺) from the intestine across the intestinal mucosa into the blood.