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| Clinical data | |
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| Trade names | Daivonex, others |
| Other names | calcipotriene (USANUS) |
| 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 |
| Identifiers | |
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| CAS Number | |
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| DrugBank |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.119.473 |
| Chemical and physical data | |
| Formula | C27H40O3 |
| Molar mass | 412.614 g·mol−1 |
| 3D model (JSmol) | |
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Calcipotriol, also known ascalcipotriene and sold under the brand nameDovonex among others, is a syntheticderivative ofcalcitriol, a form ofvitamin D. It is used in the treatment ofpsoriasis.[1]
It was patented in 1985 and approved for medical use in 1991.[2] It is on theWorld Health Organization's List of Essential Medicines.[3]
Calcipotriol is also available with the syntheticcorticosteroidbetamethasone dipropionate as the fixed-dosecombination medicationcalcipotriol/betamethasone dipropionate for the treatment ofplaque psoriasis.[4]
Chronic plaque psoriasis is the chief medical use of calcipotriol.[5] It has also been used successfully in the treatment ofalopecia areata.[6]
Hypersensitivity, use on face,hypercalcaemia, or evidence of vitamin D toxicity are the onlycontraindications 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 by frequency:[5][7][8][9]
No drug interactions are known.[7]
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 thevitamin D receptor (VDR), while being less than 1% as active as the calcitriol in regulatingcalcium 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, andT 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 cytokineTSLP bykeratinocytes, and triggeredatopic dermatitis at high concentrations.[11] This upregulation of TSLP production due to calcipotriol application is thought to be mediated through thecoactivation ofvitamin D receptor/RXRα and vitamin D receptor/RXRβ heterodimers. As psoriasis is typically thought to be partially driven byTh1/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 aTh2 response. However, it is important to note that this has not yet been confirmed.
After application and systemic uptake, calcipotriol undergoes rapidhepatic 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 tocalcitroic acid.[13]
It is sold under the brand name Dovonex in the United States, Daivonex outside North America, and Psorcutan in Germany.[citation needed]
