Calcipotriol

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-methylidenecyclohexane-1,3-diol
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a608018
Pregnancy cat.	B3 (Au), C (US)
Legal status	POM (UK) ℞-only (US)
Routes	Topical
Pharmacokinetic data
Bioavailability	5 to 6%
Metabolism	Hepatic
Excretion	Biliary
Identifiers
CAS number	112965-21-6 Y
ATC code	D05AX02
PubChem	CID 5288783
DrugBank	DB02300
ChemSpider	4450880 Y
UNII	143NQ3779B Y
KEGG	D01125 Y
ChEBI	CHEBI:50749 Y
ChEMBL	CHEMBL100918 N
Chemical data
Formula	C27H40O3
Mol. mass	412.605 g/mol
SMILES	eMolecules & PubChem
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 Y Key:LWQQLNNNIPYSNX-UROSTWAQSA-N Y
N(what is this?)  (verify)

Calcipotriol (INN) or calcipotriene (USAN) is a synthetic derivative of calcitriol or vitamin D. It is used in the treatment of psoriasis, marketed under the trade name Dovonex or Daivonex.

Mechanism

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, a patient's psoriasis lesions dramatically disappeared.^[1]

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.

Usage and efficacy

Available as a cream, ointment or scalp solution (50 µg/mL), calcipotriol is applied twice daily to plaque psoriasis on the body or scalp, but not the face. Improvement is usually detectable within 2 weeks. Most patients show some improvement, slightly more so than is seen with the use of corticosteroids alone. Tachyphylaxis does not occur, an improvement over glucocorticoid therapy.^[2]

Side effects

Calcipotriol has been shown in clinical trials to have an excellent safety profile.^[3] Reports of hypercalcemia are rare.^[4]

It is also available in combination with the synthetic glucocorticoid betamethasone as betamethasone/calcipotriol.

References

1. ^ Morimoto, S., Kumahara, Y. A patient with psoriasis cured by 1-α-hydroxyvitamin D₃. Med. J. Osaka Univ., 1985, 35:51-54
2. ^ Kragbelle, K. Treatment of psoriasis with calcipotriol and other Vitamin D analogues. J. Am. Acad. Dermatol., 1992, 27:1001-1008.
3. ^ Brunton, Laurence. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 11th ed. McGraw-Hill, 2006. p. 1664. p. 1704-5.
4. ^ Hardman et al. Hypercalcaemia associated with calcipotriol (DOVONEX) treatment. Br Med J., 1993, 306:896.

External links

• Leo Pharmaceuticals Product Monograph- Detailed information from the manufacturers, includes the blood testing recommendation (.pdf document).
• Calcipotriene information - U.S. NLM/NIH