Calcipotriol

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Calcipotriol
Calcipotriol.svg
Calcipotriol-from-xtal-Mercury-3D-balls-thin.png
Clinical data
Trade names Daivonex, Dovonex, Sorilux
Other namescalcipotriene (USAN US)
AHFS/Drugs.com Monograph
MedlinePlus a608018
License data
Pregnancy
category
  • AU:B3
Routes of
administration
Topical administration
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 5 to 6%
Metabolism Liver
Excretion Biliary
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
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.119.473 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C27H40O3
Molar mass 412.614 g·mol−1
3D model (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 Yes check.svgY
  • Key:LWQQLNNNIPYSNX-UROSTWAQSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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 ]

Contents

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 Calcipotriol/betamethasone dipropionate, a fixed-dose combination medication with the synthetic corticosteroid 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)
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 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. 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.

Related Research Articles

<span class="mw-page-title-main">Psoriasis</span> Skin disease

Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by patches of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small localized patches to complete body coverage. Injury to the skin can trigger psoriatic skin changes at that spot, which is known as the Koebner phenomenon.

Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcemia. Those with a mild increase that has developed slowly typically have no symptoms. In those with greater levels or rapid onset, symptoms may include abdominal pain, bone pain, confusion, depression, weakness, kidney stones or an abnormal heart rhythm including cardiac arrest.

<span class="mw-page-title-main">Clobetasol propionate</span> Medication

Clobetasol propionate is a corticosteroid used to treat skin conditions such as eczema, contact dermatitis, seborrheic dermatitis, and psoriasis. It is applied to the skin as a cream, ointment, or shampoo. Use should be short term and only if other weaker corticosteroids are not effective. Use is not recommended in rosacea or perioral dermatitis.

<span class="mw-page-title-main">Alopecia universalis</span> Medical condition

Alopecia universalis(AU), also known as alopecia areata universalis, is a medical condition involving the loss of all body hair, including eyebrows, eyelashes, chest hair, armpit hair, and pubic hair. It is the most severe form of alopecia areata (AA). People with the condition are usually healthy and have no other symptoms and a normal life expectancy.

<span class="mw-page-title-main">Triamcinolone</span> Steroid medication

Triamcinolone is a glucocorticoid used to treat certain skin diseases, allergies, and rheumatic disorders among others. It is also used to prevent worsening of asthma and COPD. It can be taken in various ways including by mouth, injection into a muscle, and inhalation.

<span class="mw-page-title-main">Betamethasone</span> Steroid medication

Betamethasone is a steroid medication. It is used for a number of diseases including rheumatic disorders such as rheumatoid arthritis and systemic lupus erythematosus, skin diseases such as dermatitis and psoriasis, allergic conditions such as asthma and angioedema, preterm labor to speed the development of the baby's lungs, Crohn's disease, cancers such as leukemia, and along with fludrocortisone for adrenocortical insufficiency, among others. It can be taken by mouth, injected into a muscle, or applied to the skin, typically in cream, lotion, or liquid forms.

The management of hair loss, includes prevention and treatment of alopecia, baldness, and hair thinning, and regrowth of hair.

<span class="mw-page-title-main">Calcitriol</span> Active form of vitamin D

Calcitriol is the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxycholecalciferol. It is a hormone which binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the expression of many genes. Calcitriol increases blood calcium (Ca2+) mainly by increasing the uptake of calcium from the intestines.

<span class="mw-page-title-main">Betamethasone dipropionate</span> Glucocorticoid steroid (chemical compound)

Betamethasone dipropionate is a glucocorticoid steroid with anti-inflammatory and immunosuppressive properties. It is applied as a topical cream, ointment, lotion or gel (Diprolene) to treat itching and other skin conditions such as eczema. Minor side effects include dry skin and mild, temporary stinging when applied. Betamethasone dipropionate is a "super high potency" corticosteroid used to treat inflammatory skin conditions such as dermatitis, eczema and psoriasis. It is a synthetic analog of the adrenal corticosteroids. Although its exact mechanism of action is not known, it is effective when applied topically to cortico-responsive inflammatory dermatoses. It is available as a generic medication.

<span class="mw-page-title-main">Alitretinoin</span> Chemical compound

Alitretinoin, or 9-cis-retinoic acid, is a form of vitamin A. It is also used in medicine as an antineoplastic (anti-cancer) agent developed by Ligand Pharmaceuticals. It is a first generation retinoid. Ligand gained Food and Drug Administration (FDA) approval for alitretinoin in February 1999.

<span class="mw-page-title-main">Diflorasone diacetate</span> Chemical compound and topical steroid

Diflorasone diacetate is a topical steroid that comes in the form of a cream. It is manufactured by E. Fougera & Co. and is used as an anti-inflammatory and anti-itching agent, like other topical corticosteroids. It is prescribed for psoriasis and atopic dermatitis, among other conditions. With respect to potency, it is regarded as a Class I corticosteroid [of classes I – VII] in the United States.

<span class="mw-page-title-main">Amcinonide</span> Chemical compound

Amcinonide is a topical glucocorticoid used to treat itching, redness and swelling associated with several dermatologic conditions such as atopic dermatitis and allergic contact dermatitis. Amcinonide can also be classified as a multi-functional small molecule corticosteroid, which has been approved by the FDA and is currently marketed as an ointment, lotion, or cream. It acts as both a transcription factor for responses to glucocorticoids and modulator for other transcription factors while also regulating phospholipase A2 activity.

<span class="mw-page-title-main">Halometasone</span> Chemical compound

Halometasone is a potent synthetic tri-halogenated corticosteroid for topical application possessing pronounced anti-inflammatory, antiexudative, antiepidermoplastic, antiallergic, and antipruritic properties. It has been approved in many European countries including Spain, Germany, Switzerland, Austria, Netherlands, Belgium, and Portugal and other regions such as China, Hong Kong, Turkey, Israel, South Africa and India.

In medicine, a finger tip unit (FTU) is defined as the amount of ointment, cream or other semi-solid dosage form expressed from a tube with a 5 mm diameter nozzle, applied from the distal skin-crease to the tip of the index finger of an adult. The "distal skin-crease" is the skin crease over the joint nearest the end of the finger. One FTU is enough to treat an area of skin twice the size of the flat of an adult's hand with the fingers together, i.e. a "handprint". Two FTUs are approximately equivalent to 1 g of topical steroid.

<span class="mw-page-title-main">Paricalcitol</span> Chemical compound

Paricalcitol (chemically it is 19-nor-1,25-(OH)2-vitamin D2. Marketed by Abbott Laboratories under the trade name Zemplar) is a drug used for the prevention and treatment of secondary hyperparathyroidism (excessive secretion of parathyroid hormone) associated with chronic kidney failure. It is an analog of 1,25-dihydroxyergocalciferol, the active form of vitamin D2 (ergocalciferol).

Topical steroids are the topical forms of corticosteroids. Topical steroids are the most commonly prescribed topical medications for the treatment of rash and eczema. Topical steroids have anti-inflammatory properties and are classified based on their skin vasoconstrictive abilities. There are numerous topical steroid products. All the preparations in each class have the same anti-inflammatory properties but essentially differ in base and price.

<span class="mw-page-title-main">Psoriatic onychodystrophy</span> Medical condition

Psoriatic onychodystrophy or psoriatic nails is a nail disease. It is common in those with psoriasis, with reported incidences varying from 10% to 78%. Elderly patients and those with psoriatic arthritis are more likely to have psoriatic nails.

Mark G. Lebwohl is an American dermatologist and author who is Professor and Chairman Emeritus of the Kimberly and Eric J. Waldman Department of Dermatology and the Dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai in New York City.

<span class="mw-page-title-main">Calcipotriol/betamethasone dipropionate</span> Combination drug

Calcipotriol/betamethasone dipropionate, sold under the brand name Taclonex among others, is a fixed-dose combination medication of the synthetic vitamin D3 analog calcipotriol (also known as calcipotriene) and the synthetic corticosteroid betamethasone dipropionate for the treatment of plaque psoriasis. It is used in the form of ointment, topical suspension, gel, aerosol, and foam.

<span class="mw-page-title-main">Topical glucocorticoids</span>

Topical glucocorticoids are the topical forms of glucocorticoids. Topical glucocorticoids are used in the treatment of many skin conditions. They provide anti-inflammatory, antimitotic, and immune-system suppressing actions through various mechanisms.

References

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  3. World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
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  11. Li M, Hener P, Zhang Z, Kato S, Metzger D, Chambon P (August 2006). "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. Bibcode:2006PNAS..10311736L. doi: 10.1073/pnas.0604575103 . PMC   1544239 . PMID   16880407.
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  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.