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药品详细

Cinacalcet(西那卡塞)

化学结构式图
中文名
西那卡塞
英文名
Cinacalcet
分子式
C22H22F3N
化学名
[(1R)-1-(naphthalen-1-yl)ethyl]({3-[3-(trifluoromethyl)phenyl]propyl})amine
分子量
Average: 357.412
Monoisotopic: 357.170434324
CAS号
226256-56-0
ATC分类
H05B 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Cinacalcet (INN) is a drug that acts as a calcimimetic (i.e. it mimics the action of calcium on tissues) by allosteric activation of the calcium-sensing receptor that is expressed in various human organ tissues. It is sold by Amgen under the trade name Sensipar® in North America and Australia and as Mimpara® in Europe. Cinacalcet is used to treat hyperparathyroidism (elevated parathyroid hormone levels), a consequence of parathyroid tumors and chronic renal failure.

生产厂家
  • Amgen inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Torres PU: Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism caused by chronic kidney disease. J Ren Nutr. 2006 Jul;16(3):253-8. Pubmed
  2. Padhi D, Harris R: Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. Clin Pharmacokinet. 2009;48(5):303-11. doi: 10.2165/00003088-200948050-00002. Pubmed
  3. Dong BJ: Cinacalcet: An oral calcimimetic agent for the management of hyperparathyroidism. Clin Ther. 2005 Nov;27(11):1725-51. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Naphthalenes
  • Phenylpropylamines
Substructures
  • Naphthalenes
  • Aliphatic and Aryl Amines
  • Halogen Derivatives
  • Benzene and Derivatives
  • Aromatic compounds
  • Phenylpropylamines
适应症
药理
Indication For the treatment of secondary hyperparathyroidism in patients with Chronic Kidney Disease who are on hemodialysis or peritoneal dialysis. Also for the treatment of hypercalcemia in patients with parathyroid carcinoma.
Pharmacodynamics Cinacalcet is a drug that acts as a calcimimetic (i.e. it mimics the action of calcium on tissues). Secondary hyperparathyroidism (HPT) in patients with chronic kidney disease (CKD) is a progressive disease, associated with increases in parathyroid hormone (PTH) levels and derangements in calcium and phosphorus metabolism. Increased PTH stimulates osteoclastic activity resulting in cortical bone resorption and marrow fibrosis. The goals of treatment of secondary hyperparathyroidism are to lower levels of PTH, calcium, and phosphorus in the blood, in order to prevent progressive bone disease and the systemic consequences of disordered mineral metabolism. In CKD patients on dialysis with uncontrolled secondary HPT, reductions in PTH are associated with a favorable impact on bone-specific alkaline phosphatase (BALP), bone turnover and bone fibrosis. Cinacalcet reduces calcium levels by increasing the sensitivity of the calcium sensing receptor to extracellular calcium.
Mechanism of action The calcium-sensing receptors on the surface of the chief cell of the parathyroid gland is the principal regulator of parathyroid hormone secretion (PTH). Cinacalcet directly lowers parathyroid hormone levels by increasing the sensitivity of the calcium sensing receptors to activation by extracellular calcium, resulting in the inhibition of PTH secretion. The reduction in PTH is associated with a concomitant decrease in serum calcium levels.
Absorption Rapidly absorbed following oral administration.
Volume of distribution
  • 1000 L
Protein binding Approximately 93 to 97% bound to plasma proteins.
Metabolism
Metabolism is hepatic by multiple enzymes, primarily CYP3A4, CYP2D6, and CYP1A2. After administration of a 75 mg radiolabeled dose to healthy volunteers, cinacalcet was rapidly and extensively metabolized via: 1) oxidative N-dealkylation to hydrocinnamic acid and hydroxy-hydrocinnamic acid, which are further metabolized via ß-oxidation and glycine conjugation; the oxidative N-dealkylation process also generates metabolites that contain the naphthalene ring; and 2) oxidation of the naphthalene ring on the parent drug to form dihydrodiols, which are further conjugated with glucuronic acid.

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

Substrate Enzymes Product
Cinacalcet
    		Hydrocinnamic acid Details
    Cinacalcet
      		hydroxy-hydrocinnamic acid Details
      Route of elimination Cinacalcet is metabolized by multiple enzymes, primarily CYP3A4, CYP2D6 and CYP1A2. Renal excretion of metabolites was the primary route of elimination of radioactivity.
      Half life Terminal half-life is 30 to 40 hours. The mean half-life of cinacalcet is prolonged by 33% and 70% in patients with moderate and severe hepatic impairment, respectively.
      Clearance Not Available
      Toxicity Doses titrated up to 300 mg once daily have been safely administered to patients on dialysis. Overdosage of cinacalcet may lead to hypocalcemia.
      Affected organisms
      • Humans and other mammals
      Pathways Not Available
      理化性质
      Properties
      State solid
      Experimental Properties
      Property Value Source
      water solubility Slightly soluble (in HCl salt form) Not Available
      logP 6.5 Not Available
      Predicted Properties
      Property Value Source
      water solubility 5.59e-05 g/l ALOGPS
      logP 5.57 ALOGPS
      logP 6.27 ChemAxon
      logS -6.8 ALOGPS
      pKa (strongest basic) 10.3 ChemAxon
      physiological charge 1 ChemAxon
      hydrogen acceptor count 1 ChemAxon
      hydrogen donor count 1 ChemAxon
      polar surface area 12.03 ChemAxon
      rotatable bond count 7 ChemAxon
      refractivity 100.12 ChemAxon
      polarizability 37.9 ChemAxon
      药物相互作用
      Drug Interaction
      Erythromycin The macrolide, erythromycin, may increase the serum concentration and toxicity of cinacalcet.
      Itraconazole Itraconazole may increase the effect and toxicity of cinacalcet.
      Ketoconazole Ketoconazole may increase the effect and toxicity of cinacalcet.
      Tamoxifen Cinacalcet may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
      Tamsulosin Cinacalcet, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Cinacalcet is initiated, discontinued, or dose changed.
      Telithromycin Telithromycin may reduce clearance of Cinacalcet. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Cinacalcet if Telithromycin is initiated, discontinued or dose changed.
      Tolterodine Cinacalcet may decrease the metabolism and clearance of Tolterodine. Monitor for adverse/toxic effects of Tolterodine.
      Tramadol Cinacalcet may decrease the effect of Tramadol by decreasing active metabolite production.
      Trimipramine The strong CYP2D6 inhibitor, Cinacalcet, may decrease the metabolism and clearance of Trimipramine, a CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Cinacalcet is initiated, discontinued or dose changed.
      Venlafaxine Cinacalcet, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Cinacalcet is initiated, discontinued, or dose changed.
      Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of cinacalcet by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of cinacalcet if voriconazole is initiated, discontinued or dose changed.
      Zuclopenthixol Cinacalcet, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if cinacalcet is initiated, discontinued or dose changed.
      食物相互作用
      • Food markedly increases product bioavailability.
      • Peak levels and area under curve (drug exposure) are increased (82% and 68% respectively) when product is taken with a lipid-rich meal.
      • Take with food or soon after a meal.

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