Calcipotriol

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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
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
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
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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.[1] 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.[2] 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.[3]

Calcipotriol is also available as

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)
  • Burning
  • Itchiness
  • Skin irritation
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

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]

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

Chemistry

Calcipotriol is a white to almost white crystalline compound.

References

  1. ISBN 9780198729426
    .
  2. ISBN 9783527607495
    .
  3. hdl:10665/345533
    . WHO/MHP/HPS/EML/2021.02.
  4. ^ "Taclonex- calcipotriene and betamethasone dipropionate ointment". DailyMed. 21 May 2020. Retrieved 19 October 2020.
  5. ^
    ISBN 978-0-9805790-9-3
    .
  6. PMID 22879719
    .
  7. ^ a b c d "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. PMID 4069059
    .
  11. PMID 16880407
    .
  12. PMID 23364144
    .
  13. ^ "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

  • "Calcipotriene". Drug Information Portal. U.S. National Library of Medicine.
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