| Revision as of 17:06, 10 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,071 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'ChEMBL').← Previous edit |
Latest revision as of 01:57, 12 January 2025 edit undoArthurfragoso (talk | contribs)Extended confirmed users, Template editors4,591 edits dark mode fix |
| (82 intermediate revisions by 56 users not shown) |
| Line 1: |
Line 1: |
|
|
{{Short description|Chemical compound}} |
|
|
{{cs1 config|name-list-style=vanc|display-authors=6}} |
|
{{Drugbox |
|
{{Drugbox |
|
| Verifiedfields = changed |
|
| Verifiedfields = changed |
|
|
| Watchedfields = changed |
|
| verifiedrevid = 407869516 |
|
|
|
| verifiedrevid = 459992907 |
|
| IUPAC_name = (1''R'',3''S'',5''E'')-5-{2--7a-methyl-octahydro-1''H''-inden-4-ylidene]ethylidene}-4-methylidenecyclohexane-1,3-diol |
|
|
|
| drug_name = |
|
| image = Calcipotriol.svg |
|
|
|
| type = |
|
|
| image = Calcipotriol.svg |
|
|
| image_class = skin-invert-image |
|
|
| alt = |
|
|
| caption = |
|
|
| image2 = Calcipotriol-from-xtal-Mercury-3D-balls-thin.png |
|
|
| image_class2 = bg-transparent |
|
|
| USAN = calcipotriene |
|
|
|
|
|
<!--Clinical data--> |
|
<!--Clinical data--> |
|
| tradename = |
|
| tradename = Daivonex, Dovonex, Sorilux |
|
| Drugs.com = {{drugs.com|monograph|calcitriol}} |
|
| Drugs.com = {{drugs.com|monograph|calcitriol}} |
|
| MedlinePlus = a608018 |
|
| MedlinePlus = a608018 |
|
|
| licence_EU = |
|
| pregnancy_category = B3 <small>(])</small>, C <small>(])</small> |
|
|
|
| DailyMedID = Calcipotriene |
|
| legal_UK = POM |
|
|
|
| licence_US = |
|
| legal_US = Rx-only |
|
|
|
| pregnancy_AU = B3 |
|
| routes_of_administration = Topical |
|
|
|
| pregnancy_category = |
|
|
| routes_of_administration = ] |
|
|
| ATC_prefix = D05 |
|
|
| ATC_suffix = AX02 |
|
|
|
|
|
| legal_AU = S4 |
|
|
| legal_CA = Rx-only |
|
|
| legal_UK = POM |
|
|
| legal_US = Rx-only |
|
|
| legal_status = |
|
|
|
|
|
<!--Pharmacokinetic data--> |
|
<!--Pharmacokinetic data--> |
|
| bioavailability = 5 to 6% |
|
| bioavailability = 5 to 6% |
|
| metabolism = ] |
|
| metabolism = ] |
|
| excretion = Biliary |
|
| excretion = Biliary |
|
|
|
|
|
<!--Identifiers--> |
|
<!--Identifiers--> |
|
| CASNo_Ref = {{cascite|correct|CAS}} |
|
| CAS_number_Ref = {{cascite|correct|??}} |
|
|
| CAS_number = 112965-21-6 |
|
| CAS_number_Ref = {{cascite|correct|??}} |
|
|
|
| PubChem = 5288783 |
|
| CAS_number = 112965-21-6 |
|
|
|
| IUPHAR_ligand = 2778 |
|
| ATC_prefix = D05 |
|
|
|
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
|
| ATC_suffix = AX02 |
|
|
|
| DrugBank = DB02300 |
|
| PubChem = 5288783 |
|
|
|
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
|
| DrugBank_Ref = {{drugbankcite|changed|drugbank}} |
|
|
|
| ChemSpiderID = 4450880 |
|
| DrugBank = DB02300 |
|
|
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
|
| UNII_Ref = {{fdacite|correct|FDA}} |
|
|
| UNII = 143NQ3779B |
|
| ChemSpiderID = 4450880 |
|
|
| UNII_Ref = {{fdacite|correct|FDA}} |
|
| KEGG_Ref = {{keggcite|correct|kegg}} |
|
|
| KEGG = D01125 |
|
| UNII = 143NQ3779B |
|
|
| KEGG_Ref = {{keggcite|changed|kegg}} |
|
| ChEBI_Ref = {{ebicite|correct|EBI}} |
|
|
| ChEBI = 50749 |
|
| KEGG = D01125 |
|
|
| ChEBI_Ref = {{ebicite|changed|EBI}} |
|
| ChEMBL_Ref = {{ebicite|changed|EBI}} |
|
|
| ChEMBL = 100918 |
|
| ChEBI = 50749 |
|
|
|
|
|
| ChEMBL_Ref = {{ebicite|changed|EBI}} |
|
|
|
<!--Chemical data--> |
|
| ChEMBL = <!-- blanked - oldvalue: 100918 --> |
|
|
|
| IUPAC_name = (1''R'',3''S'',5''E''<nowiki>)-5-{2--7a-methyl-octahydro-1''H''-inden-4-ylidene]ethylidene}-4-methylidenecyclohexane-1,3-diol |
|
| C=27 | H=40 | O=3 |
|
|
|
| C = 27 |
|
| molecular_weight = 412.605 g/mol |
|
|
|
| H = 40 |
|
| smiles = O1CC(\C(=C)(O)C1)=C\C=C2/CCC4(2CC4(/C=C/(O)C3CC3)C)C |
|
|
|
| O = 3 |
|
| InChI = 1/C27H40O3/c1-17(6-13-25(29)20-8-9-20)23-11-12-24-19(5-4-14-27(23,24)3)7-10-21-15-22(28)16-26(30)18(21)2/h6-7,10,13,17,20,22-26,28-30H,2,4-5,8-9,11-12,14-16H2,1,3H3/b13-6+,19-7+,21-10-/t17-,22-,23-,24+,25-,26+,27-/m1/s1 |
|
|
|
| smiles = O1CC(\C(=C)(O)C1)=C\C=C2/CCC4(2CC4(/C=C/(O)C3CC3)C)C |
|
| InChIKey = LWQQLNNNIPYSNX-UROSTWAQBW |
|
|
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
|
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
|
| StdInChI = 1S/C27H40O3/c1-17(6-13-25(29)20-8-9-20)23-11-12-24-19(5-4-14-27(23,24)3)7-10-21-15-22(28)16-26(30)18(21)2/h6-7,10,13,17,20,22-26,28-30H,2,4-5,8-9,11-12,14-16H2,1,3H3/b13-6+,19-7+,21-10-/t17-,22-,23-,24+,25-,26+,27-/m1/s1 |
|
| StdInChI = 1S/C27H40O3/c1-17(6-13-25(29)20-8-9-20)23-11-12-24-19(5-4-14-27(23,24)3)7-10-21-15-22(28)16-26(30)18(21)2/h6-7,10,13,17,20,22-26,28-30H,2,4-5,8-9,11-12,14-16H2,1,3H3/b13-6+,19-7+,21-10-/t17-,22-,23-,24+,25-,26+,27-/m1/s1 |
|
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
|
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
|
| StdInChIKey = LWQQLNNNIPYSNX-UROSTWAQSA-N |
|
| StdInChIKey = LWQQLNNNIPYSNX-UROSTWAQSA-N |
|
}} |
|
}} |
|
'''Calcipotriol''' (]) or '''calcipotriene''' (]) is a synthetic derivative of ] or ]. It is used in the treatment of ], marketed under the trade name '''Dovonex''' or '''Daivonex'''. |
|
|
|
|
|
|
|
<!-- Definition and medical uses --> |
|
==Mechanism== |
|
|
|
'''Calcipotriol''', also known as '''calcipotriene''', is a synthetic ] of ], a form of ]. It is used in the treatment of ].<ref>{{Cite book | vauthors = Prendergast B, Harrison J, Kulkarni K, Baguneid M |title=Oxford Handbook of Key Clinical Evidence |date=2016-10-27 |publisher=Oxford University Press |isbn=9780198729426 |pages=101}}</ref> It is safe for long-term application in psoriatic skin conditions.{{medcn|date=October 2021}} |
|
The efficacy of calcipotriol in the treatment of psoriasis was first noticed by the observation of patients receiving various forms of vitamin D in an osteoporosis study. Unexpectedly, a patient's psoriasis lesions dramatically disappeared.<ref>Morimoto, S., Kumahara, Y. A patient with psoriasis cured by 1-α-hydroxyvitamin D<sub>3</sub>. ''Med. J. Osaka Univ.'', '''1985''', 35:51-54</ref> |
|
|
|
|
|
|
|
<!-- Society and culture --> |
|
The precise mechanism of calcipotriol in remitting psoriasis is not well-understood. However, it has been shown to have comparable affinity with calcitriol for the vitamin D receptor (VDR), while being less than 1% as active as the calcitriol in regulating calcium metabolism. The vitamin D receptor belongs to the steroid/thyroid receptor superfamily, and is found on the cells of many different tissues including the thyroid, bone, kidney, and ]s of the immune system. T cells are known to play a role in psoriasis, and it is thought that the binding of calcipotriol to the VDR modulates the T cells gene transcription of cell differentiation and proliferation related genes. |
|
|
|
It was patented in 1985 and approved for medical use in 1991.<ref>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=452 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA452 |language=en}}</ref> It is marketed under the trade name "Dovonex" in the United States, "Daivonex" outside North America, and "Psorcutan" in Germany.{{citation needed|date=October 2021}} |
|
|
|
|
|
|
It is on the ].<ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref> |
|
==Usage and efficacy== |
|
|
|
|
|
|
|
Calcipotriol is also available as ], a fixed-dose ] with the synthetic ] ] for the treatment of ].<ref name="Taclonex ointment FDA label">{{cite web | title=Taclonex- calcipotriene and betamethasone dipropionate ointment | website=DailyMed | date=21 May 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ef43ba2d-20ce-4415-b5c2-e486b836812e | access-date=19 October 2020}}</ref> |
|
Available as a cream, ointment or scalp solution (50 ]/mL), calcipotriol is applied twice daily to plaque psoriasis on the body or scalp, but not the face. Improvement is usually detectable within 2 weeks. Most patients show some improvement, slightly more so than is seen with the use of corticosteroids alone. ] does not occur, an improvement over glucocorticoid therapy.<ref>Kragbelle, K. Treatment of psoriasis with calcipotriol and other Vitamin D analogues. ''J. Am. Acad. Dermatol.,'' '''1992''', 27:1001-1008.</ref> |
|
|
|
|
|
|
==Side effects== |
|
==Medical uses== |
|
|
Chronic plaque psoriasis is the chief medical use of calcipotriol.<ref name="AMH">{{cite book | veditors = Rossi S | isbn = 978-0-9805790-9-3 | title = Australian Medicines Handbook | place = Adelaide | publisher = The Australian Medicines Handbook Unit Trust | year = 2013 | edition = 2013 }}</ref> It has also been used successfully in the treatment of ].<ref>{{cite journal | vauthors = Kim DH, Lee JW, Kim IS, Choi SY, Lim YY, Kim HM, Kim BJ, Kim MN | title = Successful treatment of alopecia areata with topical calcipotriol | journal = Annals of Dermatology | volume = 24 | issue = 3 | pages = 341–344 | date = August 2012 | pmid = 22879719 | pmc = 3412244 | doi = 10.5021/ad.2012.24.3.341 }}</ref> |
|
|
|
|
|
|
==Contraindications== |
|
Calcipotriol has been shown in clinical trials to have an excellent safety profile.<ref>Brunton, Laurence. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 11th ed. McGraw-Hill, 2006. p. 1664. p. 1704-5.</ref> Reports of hypercalcemia are rare.<ref>Hardman ''et al.'' ] associated with calcipotriol (DOVONEX) treatment. ''Br Med J., '''1993,''' 306:896.</ref> |
|
|
|
Hypersensitivity, use on face, hypercalcaemia, or evidence of vitamin D toxicity are the only ] for calcipotriol use.<ref name = MSR/> |
|
|
|
|
|
|
Cautions include exposure to excessive natural or artificial light, due to the potential for calcipotriol to cause photosensitivity.<ref name = MSR/> |
|
It is also available in combination with the synthetic glucocorticoid ] as ]. |
|
|
|
|
|
|
==References== |
|
==Adverse effects== |
|
|
Adverse effects by frequency:<ref name = AMH/><ref name = MSR>{{cite web|title=Dovonex, Calcitrene Ointment (calcipotriene) dosing, indications, interactions, adverse effects, and more|work=Medscape Reference|publisher=WebMD|access-date=26 January 2014|url=http://reference.medscape.com/drug/dovonex-calcipotriene-topical-343541#showall}}</ref><ref name = DM>{{cite web|title=CALCIPOTRIENE (calcipotriene) solution |work=DailyMed|publisher=E. FOUGERA & CO. A division of Fougera Pharmaceuticals Inc.|date=May 2012|access-date=26 January 2014|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=fff63bc7-6b92-4080-9a11-017124d95162}}</ref><ref name = TGA>{{cite web|title=PRODUCT INFORMATION DAIVONEX® CREAM Calcipotriol 50 microgram/g|work=TGA eBusiness Services|publisher=LEO Pharma Pty Ltd|date=28 April 2011|access-date=26 January 2014|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-02886-3|format=PDF}}</ref> |
|
<references/> |
|
|
|
;Very common (> 10% frequency): |
|
|
* Burning |
|
|
* Itchiness |
|
|
* Skin irritation |
|
|
|
|
|
|
;Common (1–10% frequency): |
|
==External links== |
|
|
|
{{div col|colwidth=18em}} |
|
*- Detailed information from the manufacturers, includes the blood testing recommendation (.pdf document). |
|
|
|
* ] |
|
* - U.S. ]/] |
|
|
|
* Dry skin |
|
|
* ] |
|
|
* Peeling |
|
|
* Worsening of psoriasis including facial/scalp |
|
|
* Rash |
|
|
{{div col end}} |
|
|
|
|
|
;Uncommon (0.1–1% frequency): |
|
|
* Exacerbation of ] |
|
|
|
|
|
;Rare (< 0.1% frequency): |
|
|
{{div col|colwidth=18em}} |
|
|
* Allergic contact dermatitis |
|
|
* ] |
|
|
* ] |
|
|
* Changes in pigmentation |
|
|
* Skin atrophy |
|
|
{{div col end}} |
|
|
|
|
|
== Interactions == |
|
|
|
|
|
No drug interactions are known.<ref name = MSR/> |
|
|
|
|
|
==Pharmacology== |
|
|
|
|
|
===Mechanism of action=== |
|
|
The efficacy of calcipotriol in the treatment of psoriasis was first noticed by the observation of patients receiving various forms of vitamin D in an osteoporosis study. Unexpectedly, some patients who also had psoriasis experienced dramatic reductions in lesion counts.<ref name="Morimoto_1985">{{cite journal | vauthors = Morimoto S, Kumahara Y | title = A patient with psoriasis cured by 1 alpha-hydroxyvitamin D3 | journal = Medical Journal of Osaka University | volume = 35 | issue = 3–4 | pages = 51–54 | date = March 1985 | pmid = 4069059 }}</ref> |
|
|
|
|
|
The precise mechanism of calcipotriol in remitting psoriasis is not well understood. However, it has been shown to have comparable affinity with calcitriol for the ] (VDR), while being less than 1% as active as the calcitriol in regulating ]. The vitamin D receptor belongs to the steroid/thyroid receptor superfamily, and is found on the cells of many different tissues including the thyroid, bone, kidney, and ]s of the immune system. T cells are known to play a role in psoriasis, and it is thought that the binding of calcipotriol to the VDR modulates the T cells gene transcription of cell differentiation and proliferation related genes. |
|
|
|
|
|
In mouse studies, topical calcipotriol administration to the ear and dorsal skin led to a dose-dependent increase in the production of the epithelial cell-derived cytokine ] by ]s, and triggered ] at high concentrations.<ref>{{cite journal | vauthors = Li M, Hener P, Zhang Z, Kato S, Metzger D, Chambon P | title = Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 31 | pages = 11736–11741 | date = August 2006 | pmid = 16880407 | pmc = 1544239 | doi = 10.1073/pnas.0604575103 | doi-access = free | bibcode = 2006PNAS..10311736L }}</ref> This upregulation of TSLP production due to calcipotriol application is thought to be mediated through the ] of ]/] and vitamin D receptor/] heterodimers. As psoriasis is typically thought to be partially driven by ]/] inflammatory cytokines,<ref>{{cite journal | vauthors = Wong T, Hsu L, Liao W | title = Phototherapy in psoriasis: a review of mechanisms of action | journal = Journal of Cutaneous Medicine and Surgery | volume = 17 | issue = 1 | pages = 6–12 | date = 2013-02-01 | pmid = 23364144 | pmc = 3736829 | doi = 10.2310/7750.2012.11124 }}</ref> calcipotriol treatment at appropriate concentrations may alleviate psoriasis symptoms by repressing Th1/Th17 inflammation through TSLP production, which is linked to a ] response. However, it is important to note that this has not yet been confirmed. |
|
|
|
|
|
===Pharmacokinetics=== |
|
|
After application and systemic uptake, calcipotriol undergoes rapid ] metabolism. Calcipotriol is metabolized to MC1046 (the α,β−unsaturated ketone analog), which is subsequently metabolized to its primary metabolite, the saturated ketone analog MC1080. MC1080 is then slowly metabolized to ].<ref name=Enstilar>{{cite web | title = Enstilar (calcipotriene and betamethasone dipropionate) Foam, 0.005%/0.064% for topical use. Full Prescribing Information | url = http://enstilar.com/pdf/enstilar-pi.pdf | location = Parsippany, NJ | publisher = LEO Pharma Inc | date = 2015 | access-date = 2015-11-21 | archive-date = 2018-09-20 | archive-url = https://web.archive.org/web/20180920190124/http://enstilar.com/pdf/enstilar-pi.pdf | url-status = dead }}</ref> |
|
|
|
|
|
The metabolites of calcipotriol are less potent than the parent compound. |
|
|
|
|
|
== References == |
|
|
{{reflist}} |
|
|
|
|
|
== External links == |
|
|
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/calcipotriene | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Calcipotriene }} |
|
|
|
|
|
{{Antipsoriatics}} |
|
{{Antipsoriatics}} |
|
{{Vitamin}} |
|
{{Vitamins}} |
|
|
{{Vitamin D receptor modulators}} |
|
|
{{Portal bar | Medicine}} |
|
|
|
|
|
] |
|
] |
|
] |
|
] |
|
] |
|
] |
|
] |
|
] |
|
] |
|
] |
|
|
] |
|
|
|
|
] |
|
|
] |
|
|
] |
|
|
] |
|