Calcipotriol

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Calcipotriol
Calcipotriol.svg
Clinical data
Trade namesDaivonex, Dovonex, Sorilux
AHFS/Drugs.comMonograph
MedlinePlusa608018
Pregnancy
category
  • AU: B3
  • US: C (Risk not ruled out)
Routes of
administration
Topical
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability5 to 6%
MetabolismHepatic
ExcretionBiliary
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard100.119.473 Edit this at Wikidata
Chemical and physical data
FormulaC27H40O3
Molar mass412.605 g/mol g·mol−1
3D model (JSmol)
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Calcipotriol, also known as calcipotriene, is a synthetic derivative of calcitriol, a form of vitamin D. It is used in the treatment of psoriasis. It is safe for long-term application in psoriatic skin conditions.

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.

Medical uses[edit]

Chronic plaque psoriasis is the chief medical use of calcipotriol.[2] It has also been used successfully in the treatment of alopecia areata.[3]

Contraindications[edit]

Hypersensitivity, use on face, hypercalcaemia, or evidence of vitamin D toxicity are the only contraindications for calcipotriol use.[4]

Cautions include exposure to excessive natural or artificial light, due to the potential for calcipotriol to cause photosensitivity.[4]

Adverse effects[edit]

Adverse effects by frequency:[2][4][5][6]

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.[4]

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 suffered from psoriasis experienced dramatic reductions in lesion counts.[7]

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.[8] 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,[9] 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.[10]

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, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 452. ISBN 9783527607495.
  2. ^ a b Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
  3. ^ Kim, D. H.; Lee, J. W.; Kim, I. S.; Choi, S. Y.; Lim, Y. Y.; Kim, H. M.; Kim, B. J.; Kim, M. N. (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.
  4. ^ a b c d "Dovonex, Calcitrene Ointment (calcipotriene) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 26 January 2014.
  5. ^ "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.
  6. ^ "PRODUCT INFORMATION DAIVONEX® CREAM Calcipotriol 50 microgram/g" (PDF). TGA eBusiness Services. LEO Pharma Pty Ltd. 28 April 2011. Retrieved 26 January 2014.
  7. ^ Morimoto, S., Kumahara, Y. A patient with psoriasis cured by 1-α-hydroxyvitamin D3. Med. J. Osaka Univ., 1985, 35:51–54
  8. ^ Li, Mei; Hener, Pierre; Zhang, Zhikun; Kato, Shigeaki; Metzger, Daniel; Chambon, Pierre (2006-08-01). "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. doi:10.1073/pnas.0604575103. ISSN 0027-8424. PMC 1544239. PMID 16880407.
  9. ^ Wong, Tami; Hsu, Leon; Liao, Wilson (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. ISSN 1203-4754. PMC 3736829. PMID 23364144.
  10. ^ "Enstilar (calcipotriene and betamethasone dipropionate) Foam, 0.005%/0.064% for topical use. Full Prescribing Information" (PDF). Parsippany, NJ: LEO Pharma Inc. 2015.

External links[edit]