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Calcipotriol
Clinical data
Trade namesDaivonex, Dovonex, Sorilux
Other namescalcipotriene (USAN US)
AHFS/Drugs.comMonograph
MedlinePlusa608018
License data
Pregnancy
category
  • AU: B3
Routes of
administration		Topical administration
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability5 to 6%
MetabolismLiver
ExcretionBiliary
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 InfoCard100.119.473 Edit this at Wikidata
Chemical and physical data
FormulaC27H40O3
Molar mass412.614 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 checkY
  • Key:LWQQLNNNIPYSNX-UROSTWAQSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Calcipotriol, also known as calcipotriene, is a synthetic derivative of calcitriol, a form of vitamin D.[medical citation needed] It is used in the treatment of psoriasis.[medical citation needed] It is safe for long-term application in psoriatic skin conditions.[medical citation needed]

It was patented in 1985 and approved for medical use in 1991.[1] It is marketed under the trade name "Dovonex" in the United States, "Daivonex" outside North America, and "Psorcutan" in Germany.[citation needed]

It is on the World Health Organization's List of Essential Medicines.[2]

Calcipotriol is also available as Calcipotriol/betamethasone dipropionate, a fixed-dose combination medication with the synthetic corticosteroid betamethasone dipropionate for the treatment of plaque psoriasis.[3]

Medical uses[edit]

Chronic plaque psoriasis is the chief medical use of calcipotriol.[4] It has also been used successfully in the treatment of alopecia areata.[5]

Contraindications[edit]

Hypersensitivity, use on face, hypercalcaemia, or evidence of vitamin D toxicity are the only contraindications for calcipotriol use.[6]

Cautions include exposure to excessive natural or artificial light, due to the potential for calcipotriol to cause photosensitivity.[6]

Adverse effects[edit]

Adverse effects by frequency:[4][6][7][8]

Very common (> 10% frequency)
  • Burning
  • Itchiness
  • Skin irritation
Common (1–10% frequency)
Uncommon (0.1–1% frequency)
Rare (< 0.1% frequency)

Interactions[edit]

No drug interactions are known.[6]

Pharmacology[edit]

Mechanism of action[edit]

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.[9]

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.[10] 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,[11] 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[edit]

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.[12]

The metabolites of calcipotriol are less potent than the parent compound.

Chemistry[edit]

Calcipotriol is a white to almost white crystalline compound.

References[edit]

  1. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 452. ISBN 9783527607495.
  2. ^ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
  3. ^ "Taclonex- calcipotriene and betamethasone dipropionate ointment". DailyMed. 21 May 2020. Retrieved 19 October 2020.
  4. ^ a b Rossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
  5. ^ 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.
  6. ^ a b c d "Dovonex, Calcitrene Ointment (calcipotriene) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 26 January 2014.
  7. ^ "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.
  8. ^ "PRODUCT INFORMATION DAIVONEX® CREAM Calcipotriol 50 microgram/g" (PDF). TGA eBusiness Services. LEO Pharma Pty Ltd. 28 April 2011. Retrieved 26 January 2014.
  9. ^ 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.
  10. ^ 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): 11736–11741. Bibcode:2006PNAS..10311736L. doi:10.1073/pnas.0604575103. PMC 1544239. PMID 16880407.
  11. ^ Wong T, Hsu L, Liao W (2013-02-01). "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.
  12. ^ "Enstilar (calcipotriene and betamethasone dipropionate) Foam, 0.005%/0.064% for topical use. Full Prescribing Information" (PDF). Parsippany, NJ: LEO Pharma Inc. 2015. Archived from the original (PDF) on 2018-09-20. Retrieved 2015-11-21.

External links[edit]

  • "Calcipotriene". Drug Information Portal. U.S. National Library of Medicine.
source: https://en.wikipedia.org/wiki/Calcipotriol

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