Calcipotriol
Chemical compound
From Wikipedia, the free encyclopedia
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]
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| Trade names | Daivonex, others |
| Other names | calcipotriene (USAN US) |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a608018 |
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| Routes of administration | topical |
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| Pharmacokinetic data | |
| Bioavailability | 5 to 6% |
| Metabolism | Liver |
| Excretion | Biliary |
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| ECHA InfoCard | 100.119.473 |
| Chemical and physical data | |
| Formula | C27H40O3 |
| Molar mass | 412.614 g·mol−1 |
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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)
- Burning
- Itchiness
- Skin irritation
- Common (1–10% frequency)
- Dermatitis
- Dry skin
- Erythema
- Peeling
- Worsening of psoriasis including facial/scalp
- Rash
- Uncommon (0.1–1% frequency)
- Exacerbation of psoriasis
- Rare (< 0.1% frequency)
- Allergic contact dermatitis
- Hypercalcaemia
- Photosensitivity
- Changes in pigmentation
- Skin atrophy
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. 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]
