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药品详细

Cholecalciferol(胆)

化学结构式图
中文名
胆
英文名
Cholecalciferol
分子式
C27H44O
化学名
(1S,3Z)-3-{2-[(1R,3aS,4E,7aR)-7a-methyl-1-[(2R)-6-methylheptan-2-yl]-octahydro-1H-inden-4-ylidene]ethylidene}-4-methylidenecyclohexan-1-ol
分子量
Average: 384.6377
Monoisotopic: 384.33921603
CAS号
67-97-0
ATC分类
A11C 未知
药物类型
small molecule
阶段
approved, nutraceutical
商品名
同义名
基本介绍

Derivative of 7-dehydroxycholesterol formed by ultraviolet rays breaking of the C9-C10 bond. It differs from ergocalciferol in having a single bond between C22 and C23 and lacking a methyl group at C24. [PubChem]

生产厂家
    封装厂家
    参考
    Synthesis Reference Not Available
    General Reference
    1. Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. Pubmed
    剂型
    规格
    化合物类型
    Type small molecule
    Classes Not Available
    Substructures Not Available
    适应症
    药理
    Indication For the treatment of 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 Cholecalciferol (vitamin D3) is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, in mineralization of bone, and for the assimilation of Vitamin A. The classical manifestations of vitamin D deficiency is rickets, which is seen in children and results in bony deformaties including bowed long bones. Deficiency in adults leads to the disease osteomalacia. Both rickets and osteomalacia reflect impaired mineralization of newly synthesized bone matrix, and usually result from a combination of inadequate exposure to sunlight and decreased dietary intake of vitamin D. Common causes of vitamin D deficiency include genetic defects in the vitamin D receptor, severe liver or kidney disease, and insufficient exposure to sunlight. Vitamin D plays an important role in maintaining calcium balance and in the regulation of parathyroid hormone (PTH). It promotes renal reabsorption of calcium, increases intestinal absorption of calcium and phosphorus, and increases calcium and phosphorus mobilization from bone to plasma.
    Mechanism of action The first step involved in the activation of vitamin D3 is a 25-hydroxylation which is catalysed by the 25-hydroxylase in the liver and then by other enzymes. The mitochondrial sterol 27-hydroxylase catalyses the first reaction in the oxidation of the side chain of sterol intermediates. The active form of vitamin D3 (calcitriol) binds to intracellular receptors that then function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones, the vitamin D receptor has hormone-binding and DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and that heterodimer is what binds to DNA. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription. Calcitriol increases the serum calcium concentrations by: increasing GI absorption of phosphorus and calcium, increasing osteoclastic resorption, and increasing distal renal tubular reabsorption of calcium. Calcitriol appears to promote intestinal absorption of calcium through binding to the vitamin D receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein.
    Absorption Readily absorbed
    Volume of distribution Not Available
    Protein binding 50% to 80%
    Metabolism
    Within the liver, cholecalciferal is hydroxylated to calcidiol (25-hydroxycholecalciferol) by the enzyme 25-hydroxylase. Within the kidney, calcidiol serves as a substrate for 1-alpha-hydroxylase, yielding calcitriol (1,25-dihydroxycholecalciferol), the biologically active form of vitamin D3.

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

    Substrate Enzymes Product
    Cholecalciferol
      		(23S)-23,25-dihdroxy-24-oxovitamine D3 23-(beta-glucuronide) Details
      Route of elimination Not Available
      Half life Several weeks
      Clearance Not Available
      Toxicity Hypercalcemia - Early symptoms of hypercalcemia, include nausea and vomiting, weakness, headache, somnolence, dry mouth, constipation, metallic taste, muscle pain and bone pain. Late symptoms and signs of hypercalcemia, include polyuria, polydipsia, anorexia, weight loss, nocturia, conjunctivitis, pancreatitis, photophobia, rhinorrhea, pruritis, hyperthermia, decreased libido, elevated BUN, albuminuria, hypercholesterolemia, elevated ALT (SGPT) and AST (SGOT), ectopic calcification, nephrocalcinosis, hypertension and cardiac arrhythmias.
      Affected organisms
      • Humans and other mammals
      Pathways Not Available
      理化性质
      Properties
      State solid
      Experimental Properties
      Property Value Source
      melting point 84.5 °C PhysProp
      water solubility Insoluble Not Available
      logP 7.5 Not Available
      Predicted Properties
      Property Value Source
      water solubility 3.80e-04 g/l ALOGPS
      logP 7.98 ALOGPS
      logP 7.13 ChemAxon
      logS -6 ALOGPS
      pKa (strongest acidic) 18.38 ChemAxon
      pKa (strongest basic) -1.3 ChemAxon
      physiological charge 0 ChemAxon
      hydrogen acceptor count 1 ChemAxon
      hydrogen donor count 1 ChemAxon
      polar surface area 20.23 ChemAxon
      rotatable bond count 6 ChemAxon
      refractivity 123.22 ChemAxon
      polarizability 49.6 ChemAxon
      药物相互作用
      Drug Interaction
      Alfacalcidol 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.
      Aluminum hydroxide Vitamin D analogs such as cholecalciferol may increase the serum concentration of aluminum hydroxide. Specifically, the absorption of aluminum may be increased, leading to increased serum aluminum concentrations. Avoid chronic and/or excessive use of aluminum and aluminum-containing products in patients who are also taking vitamin D analogs. Any patients consuming such a combination should be monitored closely for aluminum status and signs/symptoms of aluminum-related toxicities.
      Calcipotriol 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). hough not specified in the prescribing information for calcipotriene, cholecalciferol, and ergocalciferol, each contains warnings regarding the potential for vitamin D toxicity.
      Calcitriol 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.
      Cholestyramine Bile acid sequestrants such as cholestyramine may decrease the serum concentration of Vitamin D analogs such as cholecalciferol. More specifically, bile acid sequestrants may impair absorption of Vitamin D analogs. Avoid concomitant administration of vitamin D analogs and bile acid sequestrants. 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.
      Colesevelam Bile acid sequestrants such as colesevelam may decrease the serum concentration of Vitamin D analogs such as cholecalciferol. More specifically, bile acid sequestrants may impair absorption of Vitamin D analogs. Avoid concomitant administration of vitamin D analogs and bile acid sequestrants. 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.
      Colestipol Bile acid sequestrants such as colestipol may decrease the serum concentration of Vitamin D analogs such as cholecalciferol. More specifically, bile acid sequestrants may impair absorption of Vitamin D analogs. Avoid concomitant administration of vitamin D analogs and bile acid sequestrants. 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.
      Doxercalciferol 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.
      Ergocalciferol 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.
      Orlistat Orlistat may decrease the serum concentration of Vitamin D analogs. More specifically, orlistat may impair absorption of Vitamin D analogs such as cholecalciferol. Monitor clinical response (plasma calcium concentrations) to orally administered vitamin D analogs closely if used with orlistat. When this combination must be used, consider administering the vitamin D analog at least 2 hours before or after the administration of orlistat.
      Paricalcitol 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.
      Sucralfate Vitamin D analogs such as cholecalciferol may increase the serum concentration of sucralfate. Specifically, the absorption of aluminum from sucralfate may be increased, leading to an increase in the serum aluminum concentration. Avoid chronic and/or excessive use of aluminum and aluminum-containing products (such as sucralfate) in patients who are also taking vitamin D analogs. Any patients consuming such a combination should be monitored closely for aluminum status and signs/symptoms of aluminum-related toxicities.
      食物相互作用
      Not Available

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