Calcipotriol

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Calcipotriol
Calcipotriol.svg
Calcipotriol-from-xtal-Mercury-3D-balls-thin.png
Clinical data
Trade names Daivonex, others
Other namescalcipotriene (USAN US)
AHFS/Drugs.com Monograph
MedlinePlus a608018
License data
Pregnancy
category
  • AU:B3
Routes of
administration 		topical
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 5 to 6%
Metabolism Liver
Excretion Biliary
Identifiers
  • (1R,3S,5E)-5-{2-[(1R,3aS,4Z,7aR)-1-[(2R,3E)-5-cyclopropyl-5-hydroxypent-3-en-2-yl]-7a-methyl-octahydro-1H-inden-4-ylidene]ethylidene}-4-methylidenecyclohexane-1,3-diol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.119.473 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C27H40O3
Molar mass 412.614 g·mol−1
3D model (JSmol)
  • O[C@@H]1CC(\C(=C)[C@@H](O)C1)=C\C=C2/CCC[C@]4([C@H]2CC[C@@H]4[C@@H](/C=C/[C@@H](O)C3CC3)C)C
  • InChI=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 Yes check.svgY
  • Key:LWQQLNNNIPYSNX-UROSTWAQSA-N Yes check.svgY
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Calcipotriol, also known as calcipotriene and sold under the brand name Dovonex among others, is a synthetic derivative of calcitriol, a form of vitamin D. It is used in the treatment of psoriasis. [1]

Contents

It was patented in 1985 and approved for medical use in 1991. [2] It is on the World Health Organization's List of Essential Medicines. [3]

Calcipotriol is also available with the synthetic corticosteroid betamethasone dipropionate as the fixed-dose combination medication calcipotriol/betamethasone dipropionate for the treatment of plaque psoriasis. [4]

Medical uses

Chronic plaque psoriasis is the chief medical use of calcipotriol. [5] It has also been used successfully in the treatment of alopecia areata. [6]

Contraindications

Hypersensitivity, use on face, hypercalcaemia, or evidence of vitamin D toxicity are the only contraindications for calcipotriol use. [7]

Cautions include exposure to excessive natural or artificial light, due to the potential for calcipotriol to cause photosensitivity. [7]

Adverse effects

Adverse effects by frequency: [5] [7] [8] [9]

Very common (> 10% frequency)
Common (1–10% frequency)
Uncommon (0.1–1% frequency)
Rare (< 0.1% frequency)

Interactions

No drug interactions are known. [7]

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. [10]

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 T cells 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 TSLP by keratinocytes, and triggered atopic dermatitis at high concentrations. [11] This upregulation of TSLP production due to calcipotriol application is thought to be mediated through the coactivation of vitamin D receptor/RXRα and vitamin D receptor/RXRβ heterodimers. As psoriasis is typically thought to be partially driven by Th1/Th17 inflammatory cytokines, [12] calcipotriol treatment at appropriate concentrations may alleviate psoriasis symptoms by repressing Th1/Th17 inflammation through TSLP production, which is linked to a Th2 response. However, it is important to note that this has not yet been confirmed.

Pharmacokinetics

After application and systemic uptake, calcipotriol undergoes rapid hepatic 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 calcitroic acid. [13]

Society and culture

Brand names

It is sold under the brand name Dovonex in the United States, Daivonex outside North America, and Psorcutan in Germany.[ citation needed ]

References

  1. ↑ Prendergast B, Harrison J, Kulkarni K, Baguneid M (27 October 2016). Oxford Handbook of Key Clinical Evidence. Oxford University Press. p. 101. ISBN   9780198729426.
  2. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 452. ISBN   9783527607495.
  3. ↑ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl: 10665/371090 . WHO/MHP/HPS/EML/2023.02.
  4. ↑ "Taclonex- calcipotriene and betamethasone dipropionate ointment". DailyMed. 21 May 2020. Retrieved 19 October 2020.
  5. 1 2 Rossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN   978-0-9805790-9-3.
  6. ↑ Kim DH, Lee JW, Kim IS, Choi SY, Lim YY, Kim HM, et al. (August 2012). "Successful treatment of alopecia areata with topical calcipotriol". Annals of Dermatology. 24 (3): 341–344. doi:10.5021/ad.2012.24.3.341. PMC   3412244 . PMID   22879719.
  7. 1 2 3 4 "Dovonex, Calcitrene Ointment (calcipotriene) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 26 January 2014.
  8. ↑ "CALCIPOTRIENE (calcipotriene) solution [E. FOUGERA & CO. A division of Fougera Pharmaceuticals Inc.]". DailyMed. E. FOUGERA & CO. A division of Fougera Pharmaceuticals Inc. May 2012. Retrieved 26 January 2014.
  9. ↑ "PRODUCT INFORMATION DAIVONEX® CREAM Calcipotriol 50 microgram/g" (PDF). TGA eBusiness Services. LEO Pharma Pty Ltd. 28 April 2011. Retrieved 26 January 2014.
  10. ↑ Morimoto S, Kumahara Y (March 1985). "A patient with psoriasis cured by 1 alpha-hydroxyvitamin D3". Medical Journal of Osaka University. 35 (3–4): 51–54. PMID   4069059.
  11. ↑ Li M, Hener P, Zhang Z, Kato S, Metzger D, Chambon P (August 2006). "Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis". Proceedings of the National Academy of Sciences of the United States of America. 103 (31) (published 1 August 2006): 11736–11741. Bibcode:2006PNAS..10311736L. doi: 10.1073/pnas.0604575103 . PMC   1544239 . PMID   16880407 – via Atypon Journals.
  12. ↑ Wong T, Hsu L, Liao W (1 February 2013). "Phototherapy in psoriasis: a review of mechanisms of action". Journal of Cutaneous Medicine and Surgery. 17 (1): 6–12. doi:10.2310/7750.2012.11124. PMC   3736829 . PMID   23364144.
  13. ↑ "Enstilar- calcipotriene and betamethasone dipropionate aerosol, foam". DailyMed. 18 October 2021. Retrieved 10 May 2025.
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