Calcitriol: Difference between revisions

{{Short description|Active form of vitamin D}}

{{Use dmy dates|date=January 2024}}

{{Infobox drug

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| image = File:Calcitriol.svg

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| image2 = Calcitriol3Dan.gif

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<!-- Clinical data -->

| pronounce = {{IPAc-en|US|ˌ|k|æ|l|s|ᵻ|ˈ|t|r|aɪ|ɒ|l}};<ref name="Dorlands">{{Citation |author=Elsevier |author-link=Elsevier |title=Dorland's Illustrated Medical Dictionary |publisher=Elsevier |url=http://dorlands.com/ |postscript=.}}</ref><ref name="Stedmans">{{Citation |author=Wolters Kluwer |author-link=Wolters Kluwer |title=Stedman's Medical Dictionary |publisher=Wolters Kluwer |url=http://stedmansonline.com/ |postscript=.}}</ref><ref name="MW_Medical">{{Citation |author=Merriam-Webster |author-link=Merriam-Webster |title=Merriam-Webster's Medical Dictionary |publisher=Merriam-Webster |url=http://unabridged.merriam-webster.com/medical/ |postscript=.}}</ref><ref name="AHD">{{Citation |author=Houghton Mifflin Harcourt |title=The American Heritage Dictionary of the English Language |publisher=Houghton Mifflin Harcourt |url=https://ahdictionary.com/ |postscript=. |access-date=25 September 2015 |archive-url=https://web.archive.org/web/20150925104737/https://ahdictionary.com/ |archive-date=25 September 2015 |url-status=dead }}</ref><ref name="MWU">{{Citation |author=Merriam-Webster |author-link=Merriam-Webster |title=Merriam-Webster's Unabridged Dictionary |publisher=Merriam-Webster |url=http://unabridged.merriam-webster.com/unabridged/ |postscript=. |access-date=25 September 2015 |archive-date=25 May 2020 |archive-url=https://web.archive.org/web/20200525084504/https://unabridged.merriam-webster.com/subscriber/login?redirect_to=%2Funabridged%2F |url-status=dead }}</ref> <br /> {{IPAc-en|UK|k|æ|l|ˈ|s|ɪ|t|r|i|ɒ|l}}

| tradename = Rocaltrol, Calcijex, Decostriol, others

| Drugs.com = {{drugs.com|monograph|calcitriol}}

| DailyMedID = Calcitriol

| pregnancy_AU = B3

| pregnancy_AU_comment =

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| routes_of_administration = [[Oral administration|By mouth]], [[intravenous]]<ref name=AHFS2019/>

| class =

| ATC_prefix = A11

| ATC_suffix = CC04

| ATC_supplemental = {{ATC|D05|AX03}}

<!-- Legal status -->

| legal_AU = S4

| legal_AU_comment =

| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->

| legal_BR_comment =

| legal_CA = Rx-only

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| legal_DE = <!-- Anlage I, II, III or Unscheduled -->

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| legal_NZ = <!-- Class A, B, C -->

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| legal_UK = POM

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| legal_US = Rx-only

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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->

| legal_UN_comment =

| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->

| protein_bound = 99.9%

| metabolism = [[Kidney]]

| metabolites =

| onset =

| elimination_half-life = 5–8 hours (adults), 27 hours (children)

| duration_of_action =

| excretion = Faeces (50%), urine (16%)

<!-- Identifiers -->

| CAS_supplemental =

| PubChem = 5280453

| IUPHAR_ligand = 2779

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| KEGG = D00129

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 17823

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| NIAID_ChemDB =

| PDB_ligand = VDX

| synonyms = 1,25-dihydroxycholecalciferol, 1alpha,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D₃, 1α,25-(OH)₂D₃, 1,25(OH)₂D<ref name="Nomen1981">{{cite journal | vauthors = | title = IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN): Nomenclature of vitamin D. Recommendations 1981 | journal = European Journal of Biochemistry | volume = 124 | issue = 2 | pages = 223–227 | date = May 1982 | pmid = 7094913 | doi = 10.1111/j.1432-1033.1982.tb06581.x | doi-access = free }}</ref>

<!-- Chemical and physical data -->

| IUPAC_name = (1''R'',3''S'')-5-[2-[(1''R'',3a''R'',7a''S'')-1-[(2''R'')-6-hydroxy-6-methyl-heptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1''H''- inden-4-ylidene]ethylidene]-4-methylidene-cyclohexane-1,3-diol

| C=27 | H=44 | O=3

| 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

| StdInChI_comment =

| density =

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<!-- Definition and physiology -->

'''Calcitriol''' is a [[hormone]] and the active form of [[vitamin D]], normally made in the [[kidney]].<ref>{{cite journal | vauthors = Plum LA, DeLuca HF | title = Vitamin D, disease and therapeutic opportunities | journal = Nature Reviews. Drug Discovery | volume = 9 | issue = 12 | pages = 941–955 | date = December 2010 | pmid = 21119732 | doi = 10.1038/nrd3318 | s2cid = 8894111 }}</ref><ref>{{cite book |title=Encyclopedia of Endocrine Diseases |date=2018 |publisher=Academic Press |isbn=9780128122006 |page=344 |url=https://books.google.com/books?id=nVh7DwAAQBAJ&pg=RA4-PA344 |language=en}}</ref><ref name="NIH-ODS-2020">{{cite web |title=Office of Dietary Supplements - Vitamin D |url=https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/ |website=ods.od.nih.gov |date=9 October 2020 |access-date=31 October 2020 |language=en}}</ref> It is also known as '''1,25-dihydroxycholecalciferol'''. It binds to and activates the [[vitamin D receptor]] in the nucleus of the cell, which then increases the expression of many genes.<ref name="Norman_2008">{{cite journal | vauthors = Norman AW | title = From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health | journal = The American Journal of Clinical Nutrition | volume = 88 | issue = 2 | pages = 491S–499S | date = August 2008 | pmid = 18689389 | doi = 10.1093/ajcn/88.2.491S | doi-access = free }}</ref> Calcitriol increases blood [[Calcium in biology|calcium]] mainly by increasing the uptake of calcium from the [[intestines]].<ref name=AHFS2019/>

<!-- Medication -->

It can be given as a medication for the treatment of [[hypocalcemia|low blood calcium]] and [[hyperparathyroidism]] due to [[kidney disease]], low blood calcium due to [[hypoparathyroidism]], [[osteoporosis]], [[osteomalacia]], and [[familial hypophosphatemia]],<ref name=AHFS2019/><ref name=BNF76/> and can be taken by mouth or by [[intravenous|injection into a vein]].<ref name=AHFS2019>{{cite web |title=Calcitriol Monograph for Professionals |url=https://www.drugs.com/monograph/calcitriol.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=9 April 2019 |language=en}}</ref> Excessive amounts or intake can result in weakness, headache, nausea, constipation, [[urinary tract infections]], and abdominal pain.<ref name=AHFS2019/><ref name=BNF76/> Serious side effects may include [[high blood calcium]] and [[anaphylaxis]].<ref name=AHFS2019/> Regular blood tests are recommended after the medication is started and when the dose is changed.<ref name=BNF76/>

<!-- History and culture -->

Calcitriol was identified as the active form of vitamin D in 1971 and the drug was approved for medical use in the United States in 1978.<ref name=AHFS2019/> It is available as a [[generic medication]].<ref name=BNF76>{{cite book|title=British national formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=1050–1051|edition=76}}</ref> In 2021, it was the 258th most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2021 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=14 January 2024 | archive-date=15 January 2024 | archive-url=https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Calcitriol - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Calcitriol | access-date = 14 January 2024}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO22nd">{{cite book | title = World Health Organization model list of essential medicines: 22nd list (2021) |url=https://iris.who.int/handle/10665/345533 | year = 2021 | hdl = 10665/345533 | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free |url-status=live |archive-url=https://web.archive.org/web/20240123194310/https://iris.who.int/bitstream/handle/10665/345533/WHO-MHP-HPS-EML-2021.02-eng.pdf?sequence=1&isAllowed=y |archive-date= Jan 23, 2024 }}</ref>

==Medical use==

Calcitriol is prescribed for:<ref name="AMH2006">{{cite book | veditors = Rossi S |title=Australian Medicines Handbook |year=2006 |location=Adelaide |isbn=978-0-9757919-2-9 |publisher=Australian Medicines Handbook Pty Ltd |title-link=Australian Medicines Handbook |last1=Rossi |first1=Simone }}</ref>

* Treatment of [[hypocalcaemia]] – [[hypoparathyroidism]], [[osteomalacia]] (adults), [[rickets]] (infants, children), [[renal osteodystrophy]], [[chronic kidney disease]]

* Treatment of [[osteoporosis]]

* Prevention of [[corticosteroid-induced osteoporosis]]

Calcitriol has been used in an ointment for the treatment of [[psoriasis]],<ref>{{cite journal | vauthors = Kircik L | title = Efficacy and safety of topical calcitriol 3 microg/g ointment, a new topical therapy for chronic plaque psoriasis | journal = Journal of Drugs in Dermatology | volume = 8 | issue = 8 Suppl | pages = s9-16 | date = August 2009 | pmid = 19702031 }}</ref> although the [[vitamin D analogue]] [[calcipotriol]] (calcipotriene) is more commonly used.<ref>{{cite journal | vauthors = Kin KC, Hill D, Feldman SR | title = Calcipotriene and betamethasone dipropionate for the topical treatment of plaque psoriasis | journal = Expert Review of Clinical Pharmacology | volume = 9 | issue = 6 | pages = 789–797 | date = June 2016 | pmid = 27089906 | doi = 10.1080/17512433.2016.1179574 | s2cid = 38261070 }}</ref> Calcitriol has also been given by mouth for the treatment of psoriasis<ref>{{cite journal | vauthors = Smith EL, Pincus SH, Donovan L, Holick MF | title = A novel approach for the evaluation and treatment of psoriasis. Oral or topical use of 1,25-dihydroxyvitamin D3 can be a safe and effective therapy for psoriasis | journal = Journal of the American Academy of Dermatology | volume = 19 | issue = 3 | pages = 516–528 | date = September 1988 | pmid = 2459166 | doi = 10.1016/S0190-9622(88)70207-8 }}</ref> and [[psoriatic arthritis]].<ref>{{cite journal | vauthors = Huckins D, Felson DT, Holick M | title = Treatment of psoriatic arthritis with oral 1,25-dihydroxyvitamin D3: a pilot study | journal = Arthritis and Rheumatism | volume = 33 | issue = 11 | pages = 1723–1727 | date = November 1990 | pmid = 2242069 | doi = 10.1002/art.1780331117 | doi-access = }}</ref> Research on the noncalcemic actions of calcitriol and other VDR-ligand analogs and their possible therapeutic applications has been reviewed.<ref>{{cite journal | vauthors = Nagpal S, Na S, Rathnachalam R | title = Noncalcemic actions of vitamin D receptor ligands | journal = Endocrine Reviews | volume = 26 | issue = 5 | pages = 662–687 | date = August 2005 | pmid = 15798098 | doi = 10.1210/er.2004-0002 | doi-access = free }}.</ref>

==Adverse effects==

The main [[adverse drug reaction]] associated with calcitriol therapy is [[hypercalcaemia]] – early symptoms include: [[nausea]], [[vomiting]], [[constipation]], [[anorexia (symptom)|anorexia]], [[apathy]], [[headache]], [[thirst]], [[pruritus]], [[sweating]], and/or [[polyuria]]. Compared to other vitamin D compounds in clinical use ([[cholecalciferol]], [[ergocalciferol]]), calcitriol has a higher risk of inducing hypercalcemia. However, such episodes may be shorter and easier to treat due to its relatively short [[elimination half-life|half-life]].<ref name="AMH2006" />

High calcitriol levels may also be seen in human disease states in patients not on supplementation. In someone with hypercalcaemia and high calcitriol levels, low intact [[parathyroid hormone]] levels are usually present.

The major conditions with hypercalcaemia due to elevated calcitriol levels are [[lymphoma]], [[tuberculosis]] and [[sarcoidosis]] where excess production occurs due to ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in [[macrophages]].<ref>{{cite journal | vauthors = Tebben PJ, Singh RJ, Kumar R | title = Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment | journal = Endocrine Reviews | volume = 37 | issue = 5 | pages = 521–547 | date = October 2016 | pmid = 27588937 | pmc = 5045493 | doi = 10.1210/er.2016-1070 }}</ref>

Other conditions producing similar findings including:

* Fungal infections; ''Pneumocystis jiroveci'', histoplasmosis, coccidioidomycosis, paracoccidioidomycosis, candidiasis

* Other granulomatous conditions; [[Granulomatosis with polyangiitis|PR3+ vasculitis]], [[Crohn's disease]], acute granulomatous pneumonia, talc granuloma, silicone-induced granuloma, BCG-associated, granulomatous hepatitis, paraffin-associated granuloma

* Genetic conditions; Williams syndrome, pseudoxanthoma elasticum, [[CYP24A1|CYP24A1 mutation]] (adult / infantile), SLC34A1 mutation

* Miscellaneous; mycobacterium avium, leprosy, lipoid pneumonia, cat scratch fever, berylliosis

Some plants contain glycosides of [[1,25-dihydroxycholecalciferol]]. Consumption of these glycosides by grazing animals leads to vitamin D toxicity, resulting in [[calcinosis]], the deposition of excessive calcium in soft tissues. Three rangeland plants, ''[[Cestrum diurnum]]'', ''[[Solanum malacoxylon]]'', and ''[[Trisetum flavescens]],'' are known to contain these glycosides. Of these, only ''C. diurnum'' is found in the U.S., mainly in Florida.<ref>{{cite web |title=Calcinogenic Glycosides |url=http://poisonousplants.ansci.cornell.edu/toxicagents/calglyco.html |website=Plants Poisonous to Livestock |publisher=Cornell Department of Animal Science |access-date=16 June 2021}}</ref>

== Mechanism of action ==

Calcitriol increases blood calcium levels ([{{chem|Ca|2+}}]) by:

* Promoting absorption of dietary calcium from the [[gastrointestinal tract]].

* Increasing [[Renal tubule|renal tubular]] reabsorption of calcium, thus reducing the loss of calcium in the urine.

* Stimulating release of calcium from bone. For this it acts on the specific type of bone cells referred to as [[osteoblasts]], causing them to release [[RANKL]], which in turn activates [[osteoclasts]].<ref>{{cite book | vauthors = Bringhurst F, Demay MB, Krane SM, Kronenberg HM |chapter=Bone and Mineral Metabolism in Health and Disease |chapter-url=http://www.accessmedicine.com/content.aspx?aID=2882031 | veditors = Fauci AS, Braunwald E, Kasper D, Hauser S, Longo D, Jameson J, Loscalzo J |title=Harrison's Principles of Internal Medicine |publisher=McGraw-Hill |edition=17th |year=2008 |isbn=978-0-07-159991-7 }}</ref>

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 {{chem|Ca|2+}}. 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).<ref name=Voet>{{cite book | vauthors = Voet D, Voet J |year=2004 |title=Biochemistry |volume=1 |chapter=Biomolecules, mechanisms of enzyme action, and metabolism |edition=3rd |pages=[https://archive.org/details/biochemistry00voet_1/page/663 663–4] |publisher=Wiley |isbn=978-0-471-25090-6 |chapter-url=https://archive.org/details/biochemistry00voet_1/page/663 }}</ref>

Many of the effects of calcitriol are mediated by its interaction with the [[calcitriol receptor]], also called the vitamin D receptor or VDR.<ref name="PMID26681795">{{cite journal | vauthors = Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G | title = Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects | journal = Physiological Reviews | volume = 96 | issue = 1 | pages = 365–408 | date = January 2016 | pmid = 26681795 | pmc = 4839493 | doi = 10.1152/physrev.00014.2015 }}</ref> 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 (biochemistry)|ligand]]-receptor complex translocates to the [[cell nucleus]], where it acts as a [[transcription factor]] promoting the expression of a gene encoding a [[Vitamin D-dependent calcium-binding protein|calcium binding protein]]. The levels of the calcium binding protein increase enabling the cells to actively transport more calcium ({{chem|Ca|2+}}) from the intestine across the [[intestinal mucosa]] into the blood.<ref name=Voet/> Alternative, ''non-genomic'' pathways may be mediated through either [[PDIA3]] or VDR.<ref>{{cite journal | vauthors = Hii CS, Ferrante A | title = The Non-Genomic Actions of Vitamin D | journal = Nutrients | volume = 8 | issue = 3 | pages = 135 | date = March 2016 | pmid = 26950144 | pmc = 4808864 | doi = 10.3390/nu8030135 | doi-access = free }}</ref>

The maintenance of electroneutrality requires that the transport of {{chem|Ca|2+}} ions catalyzed by the intestinal epithelial cells be accompanied by counterions, primarily inorganic phosphate. Thus calcitriol also stimulates the intestinal absorption of phosphate.<ref name=Voet/>

Calcitriol also inhibits the release of [[calcitonin]],<ref>{{cite journal | vauthors = Peleg S, Abruzzese RV, Cooper CW, Gagel RF | title = Down-regulation of calcitonin gene transcription by vitamin D requires two widely separated enhancer sequences | journal = Molecular Endocrinology | volume = 7 | issue = 8 | pages = 999–1008 | date = August 1993 | pmid = 8232320 | doi = 10.1210/mend.7.8.8232320 | doi-access = free }}</ref> a hormone which reduces blood calcium primarily by inhibiting calcium release from bone.<ref name=Voet/>

[[Image:Calcitriol-Synthesis.png|thumb|Calcitriol synthesis]]

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|25-hydroxyvitamin D₃ 1-alpha-hydroxylase]], a [[mitochondria]]l [[oxygenase]] and an [[enzyme]] which catalyzes the [[hydroxylation]] of [[Calcifediol|25-hydroxycholecalciferol (calcifediol)]] in the 1-alpha position.

The activity of this enzyme is stimulated by PTH. This is an important control point in [[Calcium metabolism|Ca²⁺ homeostasis]].<ref name=Voet/> Additional effects on the production of calcitriol include an increase by [[prolactin]], a hormone which stimulates [[lactogenesis]] (the formation of milk in [[mammary glands]]), a process which requires large amounts of calcium.<ref>{{cite journal | vauthors = Ajibade DV, Dhawan P, Fechner AJ, Meyer MB, Pike JW, Christakos S | title = Evidence for a role of prolactin in calcium homeostasis: regulation of intestinal transient receptor potential vanilloid type 6, intestinal calcium absorption, and the 25-hydroxyvitamin D(3) 1alpha hydroxylase gene by prolactin | journal = Endocrinology | volume = 151 | issue = 7 | pages = 2974–2984 | date = July 2010 | pmid = 20463051 | pmc = 2903940 | doi = 10.1210/en.2010-0033 }}</ref> Activity is also decreased by high levels of serum phosphate and by an increase in the production of the hormone [[FGF23]] by osteocyte cells in bone.<ref name="RodriguezFGF23">{{cite journal | vauthors = Rodríguez-Ortiz ME, Rodríguez M | title = FGF23 as a calciotropic hormone | journal = F1000Research | volume = 4 | pages = 1472 | date = 2015 | pmid = 27081473 | pmc = 4815615 | doi = 10.12688/f1000research.7189.1 | doi-access = free }}</ref>

Calcitriol is also produced outside the kidney in small amounts by many other tissues including [[placenta]] and activated [[macrophages]].<ref>{{cite journal | vauthors = Adams JS, Hewison M | title = Extrarenal expression of the 25-hydroxyvitamin D-1-hydroxylase | journal = Archives of Biochemistry and Biophysics | volume = 523 | issue = 1 | pages = 95–102 | date = July 2012 | pmid = 22446158 | pmc = 3361592 | doi = 10.1016/j.abb.2012.02.016 }}</ref>

When the drug [[alfacalcidol]] is used, 25-hydroxylation in the liver produces calcitriol as the active metabolite. This will produce greater effects than other vitamin D precursors in patients with kidney disease who have loss of the renal 1-alpha-hydroxylase.<ref name="ReferenceA"/>

===Interactive pathway map===

{{VitaminDSynthesis WP1531|highlight=Calcitriol}}

===Metabolism===

The halflife of calcitriol in the body is measured in hours, unlike its precursor calcifediol, whose halflife is measured in weeks.<ref>{{cite journal | vauthors = Brandi ML | title = Indications on the use of vitamin D and vitamin D metabolites in clinical phenotypes | journal = Clinical Cases in Mineral and Bone Metabolism | volume = 7 | issue = 3 | pages = 243–250 | date = September 2010 | pmid = 22460535 | pmc = 3213838 }}</ref> Calcitriol is inactivated by further hydroxylation to form 1,24,25-trihydroxyvitamin D, [[calcitroic acid]]. This occurs through the action of the CYP24A1 [[CYP24A1|24-hydroxylase]].<ref>{{cite journal | vauthors = Jones G, Prosser DE, Kaufmann M | title = Cytochrome P450-mediated metabolism of vitamin D | journal = Journal of Lipid Research | volume = 55 | issue = 1 | pages = 13–31 | date = January 2014 | pmid = 23564710 | pmc = 3927478 | doi = 10.1194/jlr.R031534 |doi-access=free }}</ref> Calcitroic acid is more soluble in water and is excreted in bile and urine.

==History==

It was first identified in 1971 by [[Michael F. Holick]] working in the laboratory of [[Hector DeLuca]],<ref>{{cite journal | vauthors = Holick MF, Schnoes HK, DeLuca HF, Suda T, Cousins RJ | title = Isolation and identification of 1,25-dihydroxycholecalciferol. A metabolite of vitamin D active in intestine | journal = Biochemistry | volume = 10 | issue = 14 | pages = 2799–2804 | date = July 1971 | pmid = 4326883 | doi = 10.1021/bi00790a023 }}</ref><ref name="pmid4323790">{{cite journal | vauthors = Holick MF, Schnoes HK, DeLuca HF | title = Identification of 1,25-dihydroxycholecalciferol, a form of vitamin D3 metabolically active in the intestine | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 68 | issue = 4 | pages = 803–804 | date = April 1971 | pmid = 4323790 | pmc = 389047 | doi = 10.1073/pnas.68.4.803 | doi-access = free | bibcode = 1971PNAS...68..803H }}</ref> and also by [[Anthony W. Norman|Tony Norman]] and colleagues.<ref name="pmid4325863">{{cite journal | vauthors = Norman AW, Myrtle JF, Midgett RJ, Nowicki HG, Williams V, Popják G | title = 1,25-dihydroxycholecalciferol: identification of the proposed active form of vitamin D3 in the intestine | journal = Science | volume = 173 | issue = 3991 | pages = 51–54 | date = July 1971 | pmid = 4325863 | doi = 10.1126/science.173.3991.51 | s2cid = 35236666 | bibcode = 1971Sci...173...51N }}</ref>

== Names ==

Calcitriol refers specifically to 1,25-dihydroxycholecalciferol. Because [[cholecalciferol]] already has one hydroxyl group, only two (1,25) are further specified in this nomenclature, but in fact there are three (1,3,25-triol), as indicated by the name ''calcitriol''. The 1-hydroxy group is in the alpha position, and this may be specified in the name, for instance in the abbreviation 1α,25-(OH)₂D₃.<ref name="Nomen1981"/>

Calcitriol is, strictly, the 1-hydroxylation product of [[calcifediol]] (25-OH vitamin D₃), derived from cholecalciferol (vitamin D₃), rather than the product of hydroxylations of [[ergocalciferol]] (vitamin D₂).<ref name="Nomen1981"/> 1α,25-Dihydroxyergocalciferol (ercalcitriol) should be used for the vitamin D₂ product.<ref name="Nomen1981"/> However, the terminology of 1,25-dihydroxyvitamin D, or 1,25(OH)₂D, is often used to refer to both types of active forms of vitamin D. Indeed, both bind to the vitamin D receptor and produce biological effects.<ref>{{cite journal | vauthors = Cantorna MT, Snyder L, Lin YD, Yang L | title = Vitamin D and 1,25(OH)2D regulation of T cells | journal = Nutrients | volume = 7 | issue = 4 | pages = 3011–3021 | date = April 2015 | pmid = 25912039 | pmc = 4425186 | doi = 10.3390/nu7043011 | doi-access = free }}</ref> In clinical use, the differences are unlikely to have major importance.<ref name="ReferenceA">{{cite journal | vauthors = Mazzaferro S, Goldsmith D, Larsson TE, Massy ZA, Cozzolino M | title = Vitamin D metabolites and/or analogs: which D for which patient? | journal = Current Vascular Pharmacology | volume = 12 | issue = 2 | pages = 339–349 | date = March 2014 | pmid = 23713876 | doi = 10.2174/15701611113119990024 }}</ref>

Calcitriol is marketed as a pharmaceutical for medical use under various trade names including Rocaltrol ([[Hoffman-La Roche|Roche]]), Calcijex ([[Abbott Laboratories|Abbott]]), Decostriol (Mibe, Jesalis), Vectical ([[Galderma]]), and Rolsical ([[Sun Pharmaceutical|Sun Pharma]]).

== References ==

{{Reflist}}

{{Vitamins}}

{{Vitamin D receptor modulators}}

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