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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/02/08 20:52:32」(JST)

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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)

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.^[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.

Physical and chemical properties

Calcipotriol is a white to almost white crystalline compound.

References

^ ^a ^b Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
^ 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 3412244. PMID 22879719.
^ ^a ^b ^c ^d "Dovonex, Calcitrene Ointment (calcipotriene) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 26 January 2014.
^ "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.
^ "PRODUCT INFORMATION DAIVONEX® CREAM Calcipotriol 50 microgram/g" (PDF). TGA eBusiness Services. LEO Pharma Pty Ltd. 28 April 2011. Retrieved 26 January 2014.
^ Morimoto, S., Kumahara, Y. A patient with psoriasis cured by 1-α-hydroxyvitamin D₃. Med. J. Osaka Univ., 1985, 35:51–54
^ 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 1544239. PMID 16880407.
^ 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. ISSN 1203-4754. PMC 3736829. PMID 23364144.
^ "Enstilar (calcipotriene and betamethasone dipropionate) Foam, 0.005%/0.064% for topical use. Full Prescribing Information" (PDF). Parsippany, NJ: LEO Pharma Inc. 2015.

External links

Calcipotriene information - U.S. NLM/NIH

UpToDate Contents

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1. 乾癬の治療 treatment of psoriasis
2. 妊娠時の乾癬のマネージメント management of psoriasis in pregnancy
3. 爪乾癬 nail psoriasis
4. 尋常性白斑 vitiligo
5. 高カルシウム血症の原因 etiology of hypercalcemia

English Journal

A systematic review of morphea treatments and therapeutic algorithm.

Zwischenberger BA, Jacobe HT.SourceDepartment of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas.
Journal of the American Academy of Dermatology." abstractLink="yes" alsec="jour" alterm="J Am Acad Dermatol.2011 Jun 4. [Epub ahead of print]
PMID 21645943

What is new in topical therapy for psoriasis?

Reich K, Bewley A.SourceDermatologikum Hamburg, Hamburg, Germany. reich@dermatologikum.de
Journal of the European Academy of Dermatology and Venereology : JEADV." abstractLink="yes" alsec="jour" alterm="J Eur Acad Dermatol Venereol.2011 Jun;25 Suppl 4:15-20. doi: 10.1111/j.1468-3083.2011.04061.x.
This article describes a recent development in topical therapies for psoriasis and is based on a presentation given by the authors at a satellite symposium convened during the 19th Congress of the European Academy of Dermatology and Venereology, 6-10 October 2010, in Gothenburg, Sweden. Topical ther
PMID 21507079

Japanese Journal

尋常性乾癬治療におけるドボネックズ50μg/g軟膏の併用による患者満足度およびアドヒアランスの変化についての研究

今福信一,久保田由美子,森竜樹 [他]
西日本皮膚科 74(2), 189-193, 2012-04
NAID 40019308429

治療尋常性乾癬に対するカルシポトリオール軟膏単独療法とナローバンドUVBとの併用療法との比較検討

高橋英俊,高橋一朗,飯塚一
西日本皮膚科 73(2), 180-185, 2011-04
NAID 40018816337

Related Pictures

★リンクテーブル★

リンク元	「カルシポトリオール」「カルシポトリエン」

「カルシポトリオール」

Calcipotriol
Systematic (IUPAC) name
	(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-methylidenecyclohyytyexane-1,3-diol
Clinical data
Trade names	Daivobex, Dovobex, Sorilux
AHFS/Drugs.com	monograph
MedlinePlus	a608018
Pregnancy; category	AU: B3; US: C (Risk not ruled out); ;
Legal status	AU: S4 (Prescription only); CA: ℞-only; UK: POM (Prescription only); US: ℞-only;
Routes of; administration	Topical
Pharmacokinetic data
Bioavailability	5 to 6%
Metabolism	Hepatic
Excretion	Biliary
Identifiers
CAS Number	112965-21-6
ATC code	D05AX02
PubChem	CID 5288783
IUPHAR/BPS	2778
DrugBank	DB02300
ChemSpider	4450880
UNII	143NQ3779B
KEGG	D01125
ChEBI	CHEBI:50749
ChEMBL	CHEMBL100918
Chemical data
Formula	C27H40O3
Molar mass	412.605 g/mol
	SMILES 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 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 ; Key:LWQQLNNNIPYSNX-UROSTWAQSA-N ;
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　　[★]

英: calcipotriol
商: ドボネックス
関: カルシポトリエン calcipotriene

ビタミンD3誘導体;尋常性乾癬治療

「カルシポトリエン」

　　[★]

英: calcipotriene
関: カルシポトリオール calcipotriol

合成ビタミンD

[AMH-1] 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 3412244. PMID 22879719.

[MSR-3] "Dovonex, Calcitrene Ointment (calcipotriene) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 26 January 2014.

[DM-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.

[TGA-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 1544239. 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. ISSN 1203-4754. PMC 3736829. PMID 23364144.

[Enstilar-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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calcipotriol