Calcipotriol

Calcipotriol
Clinical data
Trade names Daivonex, Dovonex, Sorilux
AHFS/Drugs.com Monograph
MedlinePlus a608018
Pregnancy
category
  • AU: B3
  • US: C (Risk not ruled out)
Routes of
administration		 Topical
ATC code D05AX02 (WHO)
Legal status
Legal status
Pharmacokinetic data
Bioavailability 5 to 6%
Metabolism Hepatic
Excretion Biliary
Identifiers
CAS Number 112965-21-6 YesY
PubChem (CID) 5288783
IUPHAR/BPS 2778
DrugBank DB02300 YesY
ChemSpider 4450880 YesY
UNII 143NQ3779B YesY
KEGG D01125 YesY
ChEBI CHEBI:50749 YesY
ChEMBL CHEMBL100918 N
ECHA InfoCard 100.119.473
Chemical and physical data
Formula C27H40O3
Molar mass 412.605 g/mol
3D model (Jmol) Interactive image
 NYesY (what is this?)  (verify)

Calcipotriol (INN) or calcipotriene (USAN) is a synthetic derivative of calcitriol, a form of vitamin D. It is used in the treatment of psoriasis, marketed under the trade name "Dovonex" in the United States, "Daivonex" outside of North America, and "Psorcutan" in Germany. This medication is safe for long-term application in psoriatic skin conditions.

Medical uses

Chronic plaque psoriasis is the chief medical use of calcipotriol.[1] It has also been used successfully in the treatment of alopecia areata.[2]

Contraindications

Hypersensitivity, use on face, hypercalcaemia, or evidence of vitamin D toxicity are the only contraindications for calcipotriol use.[3]

Cautions include exposure to excessive natural or artificial light, due to the potential for calcipotriol to cause photosensitivity.[3]

Adverse effects

Adverse effects by frequency:[1][3][4][5]

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

Interactions

No drug interactions are known.[3]

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 suffered from psoriasis experienced dramatic reductions in lesion counts.[6]

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.[7] 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,[8] 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.[9]

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

Chemistry

Calcipotriol is a white to almost white crystalline compound.

References

  1. 1 2 Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
  2. ↑ 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 3412244Freely accessible. PMID 22879719.
  3. 1 2 3 4 "Dovonex, Calcitrene Ointment (calcipotriene) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 26 January 2014.
  4. ↑ "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.
  5. ↑ "PRODUCT INFORMATION DAIVONEX® CREAM Calcipotriol 50 microgram/g" (PDF). TGA eBusiness Services. LEO Pharma Pty Ltd. 28 April 2011. Retrieved 26 January 2014.
  6. ↑ Morimoto, S., Kumahara, Y. A patient with psoriasis cured by 1-α-hydroxyvitamin D3. Med. J. Osaka Univ., 1985, 35:51–54
  7. ↑ 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 1544239Freely accessible. PMID 16880407.
  8. ↑ 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 3736829Freely accessible. PMID 23364144.
  9. ↑ "Enstilar (calcipotriene and betamethasone dipropionate) Foam, 0.005%/0.064% for topical use. Full Prescribing Information" (PDF). Parsippany, NJ: LEO Pharma Inc. 2015.
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