用户名： 密   码：
注册 | 忘记密码？
药品详细

Candesartan(坎地沙坦)

化学结构式图
中文名
坎地沙坦
英文名
Candesartan
分子式
C24H20N6O3
化学名
2-ethoxy-1-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-1,3-benzodiazole-7-carboxylic acid
分子量
Average: 440.454
Monoisotopic: 440.159688536
CAS号
139481-59-7
ATC分类
C09C 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Candesartan is an angiotensin-receptor blocker (ARB) that may be used alone or with other agents to treat hypertension. It is administered orally as the prodrug, candesartan cilexetil, which is rapidly converted to its active metabolite, candesartan, during absorption in the gastrointestinal tract. Candesartan lowers blood pressure by antagonizing the renin-angiotensin-aldosterone system (RAAS); it competes with angiotensin II for binding to the type-1 angiotensin II receptor (AT1) subtype and prevents the blood pressure increasing effects of angiotensin II. Unlike angiotensin-converting enzyme (ACE) inhibitors, ARBs do not have the adverse effect of dry cough. Candesartan may be used to treat hypertension, isolated systolic hypertension, left ventricular hypertrophy and diabetic nephropathy. It may also be used as an alternative agent for the treatment of heart failure, systolic dysfunction, myocardial infarction and coronary artery disease.

生产厂家
  • Astrazeneca pharmaceuticals lp
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Pocock S: Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003 Sep 6;362(9386):759-66. Pubmed
  2. Mendis B, Page SR: Candesartan: widening indications for this angiotensin II receptor blocker? Expert Opin Pharmacother. 2009 Aug;10(12):1995-2007. Pubmed
  3. Baguet JP, Barone-Rochette G, Neuder Y: Candesartan cilexetil in the treatment of chronic heart failure. Vasc Health Risk Manag. 2009;5(1):257-64. Epub 2009 Apr 8. Pubmed
  4. Bader, M. (2004). Renin-angiotensin-aldosterone system. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (pp. 810-814). Berlin, Germany: Springer.
  5. Stanfield, C.L., & Germann, W.J. (2008). Principles of human physiology (3 rd ed.). San Francisco, CA: Pearson Education, Inc.
剂型
规格
化合物类型
Type small molecule
Classes
  • Biphenyltetrazoles and Derivatives
Substructures
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Acetates
  • Benzoates
  • Benzimidazoles
  • Phenylpropenes
  • Ethers
  • Benzene and Derivatives
  • Biphenyl and Derivatives
  • Biphenyltetrazoles and Derivatives
  • Carboxylic Acids and Derivatives
  • Tetrazoles
  • Imidazoles
  • Phenyltetrazoles and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Imines
  • Benzoyl Derivatives
  • Cyanamides
适应症
药理
Indication May be used as a first line agent to treat uncomplicated hypertension, isolated systolic hypertension and left ventricular hypertrophy. May be used as a first line agent to delay progression of diabetic nephropathy. Candesartan may be also used as a second line agent in the treatment of congestive heart failure, systolic dysfunction, myocardial infarction and coronary artery disease in those intolerant of ACE inhibitors.
Pharmacodynamics Candesartan cilexetil is an ARB prodrug that is rapidly converted to candesartan, its active metabolite, during absorption from the gastrointestinal tract. Candesartan confers blood pressure lowering effects by antagonizing the hypertensive effects of angiotensin II via the RAAS. RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from granular cells of the juxtaglomerular apparatus in the kidneys. Renin cleaves circulating angiotensinogen to angiotensin I, which is cleaved by angiotensin converting enzyme (ACE) to angiotensin II. Angiotensin II increases blood pressure by increasing total peripheral resistance, increasing sodium and water reabsorption in the kidneys via aldosterone secretion, and altering cardiovascular structure. Angiotensin II binds to two receptors: type-1 angiotensin II receptor (AT1) and type-2 angiotensin II receptor (AT2). AT1 is a G-protein coupled receptor (GPCR) that mediates the vasoconstrictive and aldosterone-secreting effects of angiotensin II. Studies performed in recent years suggest that AT2 antagonizes AT1-mediated effects and directly affects long-term blood pressure control by inducing vasorelaxation and increasing urinary sodium excretion. Angiotensin receptor blockers (ARBs) are non-peptide competitive inhibitors of AT1. ARBs block the ability of angiotensin II to stimulate pressor and cell proliferative effects. Unlike ACE inhibitors, ARBs do not affect bradykinin-induced vasodilation. The overall effect of ARBs is a decrease in blood pressure.
Mechanism of action Candesartan selectively blocks the binding of angiotensin II to AT1 in many tissues including vascular smooth muscle and the adrenal glands. This inhibits the AT1-mediated vasoconstrictive and aldosterone-secreting effects of angiotensin II and results in an overall decrease in blood pressure. Candesartan is greater than 10,000 times more selective for AT1 than AT2. Inhibition of aldosterone secretion may increase sodium and water excretion while decreasing potassium excretion.
Absorption Following administration of the candesartan cilexetil prodrug, the absolute bioavailability of candesartan was estimated to be 15%. Food with a high fat content has no affect on the bioavailability of candesartan from candesartan cilexetil.
Volume of distribution
  • 0.13 L/kg
Protein binding Candesartan is highly bound to plasma proteins (>99%) and does not penetrate red blood cells.
Metabolism
The prodrug candesartan cilexetil undergoes rapid and complete ester hydrolysis in the intestinal wall to form the active drug, candesartan. Elimination of candesartan is primarily as unchanged drug in the urine and, by the biliary route, in the feces. Minor hepatic metabolism of candesartan (<20%)occurs by O-deethylation via cytochrome P450 2C9 to form an inactive metabolite. Candesartan undergoes N-glucuronidation in the tetrazole ring by uridine diphosphate glucuronosyltransferase 1A3 (UGT1A3). O-glucuronidation may also occur. 75% of candesartan is excreted as unchanged drug in urine and feces.

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

Substrate Enzymes Product
Candesartan
O-Deethylated candesartan Details
Candesartan
Candesartan N2-glucuronide Details
Candesartan
Candesartan O-glucuronide Details
Route of elimination When candesartan is administered orally, about 26% of the dose is excreted unchanged in urine. Candesartan is mainly excreted unchanged in urine and feces (via bile).
Half life Approximately 9 hours.
Clearance
  • 0.37 mL/min/kg
Toxicity No lethality was observed in acute toxicity studies in mice, rats and dogs given single oral doses of up to 2000 mg/kg of candesartan cilexetil or in rats given single oral doses of up to 2000 mg/kg of candesartan cilexetil in combination with 1000 mg/kg of hydrochlorothiazide. In mice given single oral doses of the primary metabolite, candesartan, the minimum lethal dose was greater than 1000 mg/kg but less than 2000 mg/kg.
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
logP 6.1 Not Available
Predicted Properties
Property Value Source
water solubility 7.71e-03 g/l ALOGPS
logP 4.02 ALOGPS
logP 5.05 ChemAxon
logS -4.8 ALOGPS
pKa (strongest acidic) 2.97 ChemAxon
pKa (strongest basic) 1.71 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 7 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 118.81 ChemAxon
rotatable bond count 7 ChemAxon
refractivity 134.92 ChemAxon
polarizability 45.35 ChemAxon
药物相互作用
Drug Interaction
Amiloride Increased risk of hyperkalemia
Drospirenone Increased risk of hyperkalemia
Lithium The ARB increases serum levels of lithium
Potassium Increased risk of hyperkalemia
Spironolactone Increased risk of hyperkalemia
Tobramycin Increased risk of nephrotoxicity
Trandolapril The angiotensin II receptor blocker, Candesartan, may increase the adverse effects of Trandolapril.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Triamterene Increased risk of hyperkalemia
食物相互作用
  • Administer on a regular basis, at about the same time each day.
  • Take without regard to meals.

返回 | 收藏