Calcitriol psoriasis

Vitamin D analogues (calcipotriol, calcitriol, and tacalcitol) are also frequently selected as initial pharmacotherapy in the management of mild to moderate psoriasis.2 These inhibit keratinocyte differentiation and proliferation and maybe antiinflammatory.2 Unlike corticosteroids, tachyphylaxis does not occur with prolonged use. Clearance of lesions should occur after 4 to 6 weeks of treatment.2 Lack of response by 8 weeks... 

Calcitriol and tacalcitol are other vitamin D derivatives that have been studied for treatment of psoriasis. 

Posner and coworkers have prepared a series of semi-synthetic and synthetic ether and ester-linked dimers that were found to have potent anti-proliferative and antitumour activities in vitro. Some of these trioxane dimers were found to be as antiproliferative as calcitriol, the hormonally active form of vitamin D, which is used to treat psoriasis, a skin disorder characterized by uncontrolled cell prohferation. Of the semi synthetic dimers, a polyethylene glycol-linked dimer 107, with S-stereochemistry at both of the lactol acetal positions, was found to be very anti-proliferative and showed activity against leukaemia and colon cancer cell hues in the National Cancer Institute (NCI), USA 60-cell line assay. 

Calcipotriol is a vitamin D3 derivative which is used as a topical agent in the treatment of psoriasis. Although not completely elucidated its mechanism of action seems to be based on inhibition of the proliferation and stimulation of the differentiation of epidermal keratinocytes. Adverse effects include irritation of the skin but also urticarial reactions. Calcipotriol has 100 fold less vitamin D activity as its active vitamin D3 metabolite calcitriol. However, calcipotriol in overdose can cause symptoms of hypercalcemia. 

Calcipotriene (Dovonex), a synthetic vitamin D3 derivative, is indicated for the treatment of moderate plaque psoriasis. Its mechanism of action is unknown, although it competes for calcitriol receptors on keratinocytes and normalizes differentiation. It also has a variety of immunomodulatory effects in the skin. Although the drug can cause local irritation, the most serious toxicities are hypercalciuria and hypercalcemia, which are usually reversible. 

The discovery that vitamin D3 (1), also called calciol [I], is actually a pro-hormone and not a vitamin as previously assumed has induced intense worldwide research activities within the last 20 years. Nowadays, it is known that the prohormone is transformed in liver and kidney into physiologically much more active metabolites by hydroxylation. In particular, the la,25-dihy-droxylated derivative, calcitriol (3), performs a key function in the regulation of different physiological events [2]. Some hydroxylated vitamin D derivatives and structural analogs are currently being clinically tested as drugs for the treatment of a range of human diseases such as cancer, psoriasis or immune defects. 

Calcitriol induces terminal differentiation of skin keratinocytes in culture, an action that has been exploited in the treatment of psoriasis (Section 3.6.2). In keratinocytes in culture, both calcium and calcitriol are required for differentiation. Cells lacking the calcium-sensing receptor or phospholipase C-y 1 fail to differentiate in response to calcium or calcitriol, suggesting that in... 

Topical calcipotriol (a vitamin D analogue) is an effective and safe treatment for mild to moderate psoriasis vulgaris. Its mode of action is identical to that of 1,25-dihydroxycolecalciferol (calcitriol). 

The efficacy, safety, and tolerability of twice-daily calcitriol ointment 3 micrograms/g (n — 60) has been investigated and compared with 0.25-2% dithranol cream (once daily for 30 minutes n = 54) in an 8-week prospective, randomized, open, parallel-group trial in 114 patients with plaque psoriasis (53). Skin irritation was reported by three patients who used calcitriol and by 39% of those who used dithranol. Three patients who used calcitriol and four who used dithranol reported adverse effects on the skin (pruritus, erythema, rash, dry skin, eczema). One patient with 75% skin involvement used 3.38 mg of calcitriol over 56 days (about 140 g of ointment per week without any effect on serum calcium). 

Hutchinson PE, Marks R, White J. The efficacy, safety and tolerance of calcitriol 3 microg/g ointment in the treatment of plaque psoriasis a comparison with short-contact dithra-nol. Dermatology 2000 201(2) 139 5. 

Vitamin D has recently found an association with psoriasis, a common disease of the skin. Psoriasis is not curable, but a variety of skin ointments can reduce the severity of the skin lesions. One of these ointments is a chemical analogue of vitamin D called calcipotriene. Calcipotriene was developed after initial observations that oral or topical calcitriol was effective against the disease. The drug results in improvement in 60% of patients (Greaves and Weinstein, 1995). 

Caldpotriene. Calcipotriene. (la.3j3.SZ7 .22 .245l-24-cyclopropyl-9.IO-secochola-.5.7.IO(l9).22-teuaene-l,3. 24-triul. calciputriol (Dovonex). is a. synthetic vitamin D< analogue indicated for topical application in the treatment of moderate plaque psoriasis. It has the same affinity for the vitamin D receptor as calcitriol. but its effect on calcium metabolism is 100 to 200 times less. Calcipotriene inhibits epidermal cell proliferation and enhances cell differentia-... 

Topical treatments of first choice for mild to moderate psoriasis include keratolytics, corticosteroids, vitamin D analogues (calcipotriene, calcitriol, and tacalcitol), and tazarotene. The systemic treatment of first choice for moderate to severe psoriasis is acitretin. See Tables 96-2 and 96-3 for topical and systemic psoriasis treatment guidelines. 

Calcitriol (1,25-dihydroxyvitamin D3) is another analogue used in the treatment of mild to moderate plaque psoriasis. As demonstrated in several open-label or randomized, double-blind, controlled trials, calcitriol is effective in improving or clearing psoriatic plaques. A 0.03% formulation showed clearance or considerable improvement in 89% of patients. ... 

Langner A, Stapor W, Ambroziak M. Efficacy and tolerance of topical calcitriol 3 microg g(-1) in psoriasis treatment a review of our experience in Poland. Br J Dermatol 2001 144(Suppl 58) 11—16. 

Positive effects of orally administered calcitriols were initially noted concerning the cutaneous symptoms of psoriasis in a patient who was orally treated with 1,25 (OH)2D3 for osteoporosis [171]. This finding led to a series of clinical trials with systemic l,25(OH)2D3, l,25(OH)2D3 precursors or l,25(OH)2D3 analogs in psoriasis. The majority of these studies demonstrated good and partially excellent clinical efficacy of calcitriols in this disease [172-177]. In linear scleroderma, another dermatological indication, systemic application of l,25(OH)2D3 lead to beneficial effects in five of seven pediatric patients treated [178]. 

Structural modifications of the calcitriol side-chain lead to changes in the biological activity profile of the respective compound series [191]. Introduction of the 22,23-double bond, transposition of the 25-OH group to the 24-position and connection of the terminal methyl groups of the side-chain afforded the so far clinically most relevant calcitriol analog, MC 903, from the Danish pharma manufacturer Leo Pharmaceutical Products [192].MC903has been successfully applied for the topical treatment of psoriasis [193] for a rather long time. 

Lebwohl, M. (2002) Vitamin D and topical therapy. Cutis, 70 (5 Suppl), 5-8. Kowalzick, L. (2001) Clinical experience with topical calcitriol (1,25-dihydroxyvitamin D3) in psoriasis. The British Journal of Dermatology, 144 (Suppl 58), 21-25. 

The VDR is distributed widely throughout the body, and calcitriol actions extend well beyond calcium homeostasis. For example, calcitriol and synthetic analogs have been evaluated as antiproliferative agents for therapy of skin diseases fe.g., psoriasis) and cancer. 

The steroid hormone l/ ,25-dihydroxyvitamin D3 (l/ ,25-(OH)2-D3, calcitriol, 158) is the bioactive metabolite of vitamin D3. This B-ring-seco-steroid plays an important role in the regulation of mineral metabolism and finds application in the treatment of osteodystrophy due to renal failure, rickets, osteoporosis, and psoriasis. The bromoolefin 156 was subjected to sequential metallation and transmetallation to give the corresponding... 

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