用户名： 密   码：
注册 | 忘记密码？
药品详细

Calcitriol(骨化三醇)

化学结构式图
中文名
骨化三醇
英文名
Calcitriol
分子式
C27H44O3
化学名
(1R,3S,5Z)-5-{2-[(1R,3aS,4E,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-octahydro-1H-inden-4-ylidene]ethylidene}-4-methylidenecyclohexane-1,3-diol
分子量
Average: 416.6365
Monoisotopic: 416.329045274
CAS号
32222-06-3
ATC分类
A11C 未知;D05A 未知
药物类型
small molecule
阶段
approved, nutraceutical
商品名
同义名
基本介绍

Calcitriol or 1,25-dihydroxycholecalciferol (abbreviated 1,25-(OH)2-D3) is the active form of vitamin D found in the body (vitamin D3). Calcitriol is marketed under various trade names including Rocaltrol (Roche), Calcijex (Abbott) and Decostriol (Mibe, Jesalis). It is produced in the kidneys via 25-hydroxyvitamin D-1 α-hydroxylase by conversion from 25-hydroxycholecalciferol (calcidiol). This is stimulated by a decrease in serum calcium, phosphate (PO43−) and parathyroid hormone (PTH) levels. It regulates calcium levels by increasing the absorption of calcium and phosphate from the gastrointestinal tract, increasing calcium and phosphate reabsorption in the kidneys and inhibiting the release of PTH. Calcitriol is also commonly used as a medication in the treatment of hypocalcemia and osteoporosis.

生产厂家
  • Abbott laboratories hosp products div
  • Akorn inc
  • App pharmaceuticals llc
  • Fresenius medical care north america
  • Galderma laboratories lp
  • Genix therapeutics inc
  • Hospira inc
  • Luitpold pharmaceuticals inc
  • Lyne laboratories inc
  • Roxane laboratories inc
  • Teva parenteral medicines inc
  • Teva pharmaceuticals usa inc
  • Validus pharmaceuticals llc
封装厂家
参考
Synthesis Reference Not Available
General Reference Not Available
剂型
规格
化合物类型
Type small molecule
Classes Not Available
Substructures Not Available
适应症
药理
Indication Used to treat vitamin D deficiency or insufficiency, refractory rickets (vitamin D resistant rickets), familial hypophosphatemia and hypoparathyroidism, and in the management of hypocalcemia and renal osteodystrophy in patients with chronic renal failure undergoing dialysis. Also used in conjunction with calcium in the management and prevention of primary or corticosteroid-induced osteoporosis.
Pharmacodynamics Calcitriol, a pharmaceutical form of vitamin D, has anti-osteoporotic, immunomodulatory, anticarcinogenic, antipsoriatic, antioxidant, and mood-modulatory activities. Calcitriol has been found to be effective in the treatment of psoriasis when applied topically. Calcitriol has been found to induce differentiation and/or inhibit cell proliferation in a number of malignant cell lines including human prostate cancer cells. Vitamin D deficiency has long been suspected to increase the susceptibility to tuberculosis. The active form of calcitriol, 1,25-(OH)2-D3, has been found to enhance the ability of mononuclear phagocytes to suppress the intracellular growth of Mycobacterium tuberculosis. 1,25-(OH)2-D3 has demonstrated beneficial effects in animal models of such autoimmune diseases as rheumatoid arthritis. It has also been found to induce monocyte differentiation and to inhibit lymphocyte proliferation and production of cytokines, including interleukin IL-1 and IL-2, as well as to suppress immunoglobulin secretion by B lymphocytes. Vitamin D appears to demonstrate both immune-enhancing and immunosuppressive effects.
Mechanism of action The mechanism of action of calcitriol in the treatment of psoriasis is accounted for by their antiproliferative activity for keratinocytes and their stimulation of epidermal cell differentiation. The anticarcinogenic activity of the active form of Calcitriol appears to be correlated with cellular vitamin D receptor (VDR) levels. Vitamin D receptors belong to the superfamily of steroid-hormone zinc-finger receptors. VDRs selectively bind 1,25-(OH)2-D3 and retinoic acid X receptor (RXR) to form a heterodimeric complex that interacts with specific DNA sequences known as vitamin D-responsive elements. VDRs are ligand-activated transcription factors. The receptors activate or repress the transcription of target genes upon binding their respective ligands. It is thought that the anticarcinogenic effect of Calcitriol is mediated via VDRs in cancer cells. The immunomodulatory activity of calcitriol is thought to be mediated by vitamin D receptors (VDRs) which are expressed constitutively in monocytes but induced upon activation of T and B lymphocytes. 1,25-(OH)2-D3 has also been found to enhance the activity of some vitamin D-receptor positive immune cells and to enhance the sensitivity of certain target cells to various cytokines secreted by immune cells.
Absorption Rapidly absorbed from the intestine.
Volume of distribution Not Available
Protein binding 99.9%
Metabolism
The first pathway involves 24-hydroxylase activity in the kidney; this enzyme is also present in many target tissues which possess the vitamin D receptor such as the intestine. The end product of this pathway is a side chain shortened metabolite, calcitroic acid. The second pathway involves the conversion of calcitriol via the stepwise hydroxylation of carbon-26 and carbon-23, and cyclization to yield ultimately 1a,25R(OH)2-26,23S-lactone D3. The lactone appears to be the major metabolite circulating in humans.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Calcitriol
    		Calcitroic acid Details
    Route of elimination Enterohepatic recycling and biliary excretion of calcitriol occur. The metabolites of calcitriol are excreted primarily in feces. Cumulative excretion of radioactivity on the sixth day following intravenous administration of radiolabeled calcitriol averaged 16% in urine and 49% in feces.
    Half life 5-8 hours
    Clearance
    • 15.3 mL/hr/kg [pediatric patients (age range: 1.8 to 16 years) undergoing peritoneal dialysis receiving dose of 10.2 ng/kg (SD 5.5 ng/kg) for 2 months]
    Toxicity LD50 (oral, rat) = 620 μg/kg; LD50 (intraperitoneal, rat) > 5 mg/kg; Overdose evident in elevated blood calcium levels causing symptoms of anorexia, nausea and vomiting, polyuria, polydipsia, weakness, pruritus, and nervousness, potentially with irreversible calcification of soft tissue in the kidney and liver.
    Affected organisms
    • Humans and other mammals
    Pathways Not Available
    理化性质
    Properties
    State solid
    Experimental Properties
    Property Value Source
    melting point 113 °C PhysProp
    water solubility Insoluble Not Available
    logP 5 Not Available
    Predicted Properties
    Property Value Source
    water solubility 6.67e-03 g/l ALOGPS
    logP 5.51 ALOGPS
    logP 4.35 ChemAxon
    logS -4.8 ALOGPS
    pKa (strongest acidic) 14.39 ChemAxon
    pKa (strongest basic) -1.3 ChemAxon
    physiological charge 0 ChemAxon
    hydrogen acceptor count 3 ChemAxon
    hydrogen donor count 3 ChemAxon
    polar surface area 60.69 ChemAxon
    rotatable bond count 6 ChemAxon
    refractivity 126.53 ChemAxon
    polarizability 51.02 ChemAxon
    药物相互作用
    Drug Interaction
    Cholecalciferol Vitamin D analogs may enhance the adverse/toxic effect of other Vitamin D analogs. Avoid combined use of multiple vitamin D analogs (at pharmacologic doses). Prescribing information for calcitriol, doxercalciferol, paricalcitol, and alfacalcidol each specifically cautions against such combined use. Though not specified in the prescribing information for calcipotriene, cholecalciferol, and ergocalciferol, each contains warnings regarding the potential for vitamin D toxicity.
    Colesevelam Bile acid sequestrants such as colesevelam may decrease the serum concentration of Vitamin D Analogs. More specifically, bile acid sequestrants may impair absorption of Vitamin D Analogs. Avoid concomitant administration of vitamin D analogs and bile acid sequestrants (e.g., cholestyramine). Monitor plasma calcium concentrations in patients receiving combined therapy with these agents. This is particularly important in patients receiving higher doses of a bile acid sequestant (i.e., 30 g/day or more of cholestyramine or equivalent) or in patients experiencing bile acid sequestrant-induced steatorrhea. Specific recommendations regarding the separation of administration of these agents are not defined; however, it would seem prudent to separate the administration of these agents by several hours to minimize the potential risk of interaction. Similar precautions do not apply to parenterally administered vitamin D analogs.
    Telithromycin Telithromycin may reduce clearance of Calcitriol. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Calcitriol if Telithromycin is initiated, discontinued or dose changed.
    Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of calcitriol by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of calcitriol if voriconazole is initiated, discontinued or dose changed.
    食物相互作用
    Not Available

    返回 | 收藏