Tìm theo
Candesartan
Các tên gọi khác (6 ) :
  • 2-Ethoxy-1-(P-(O-1H-tetrazol-5-ylphenyl)benzyl)-7-benzimidazolecarboxylic acid
  • 2-Ethoxy-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylic acid
  • 2-Ethoxy-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4ethyl]}-1H-benzimidazole-7-carboxylic acid
  • Blopress
  • Candesartan cilexetil
  • CV-11974
Thuốc tim mạch
Thuốc Gốc
Small Molecule
CAS: 139481-59-7
ATC: C09CA06
ĐG : A-S Medication Solutions LLC , http://orders.a-smeds.com
CTHH: C24H20N6O3
PTK: 440.454
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.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C24H20N6O3
Phân tử khối
440.454
Monoisotopic mass
440.159688536
InChI
InChI=1S/C24H20N6O3/c1-2-33-24-25-20-9-5-8-19(23(31)32)21(20)30(24)14-15-10-12-16(13-11-15)17-6-3-4-7-18(17)22-26-28-29-27-22/h3-13H,2,14H2,1H3,(H,31,32)(H,26,27,28,29)
InChI Key
InChIKey=HTQMVQVXFRQIKW-UHFFFAOYSA-N
IUPAC Name
2-ethoxy-1-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-1,3-benzodiazole-7-carboxylic acid
Traditional IUPAC Name
candesartan
SMILES
CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NNN=N1
Độ hòa tan
7.71e-03 g/l
logP
6.1
logS
-4.8
pKa (strongest acidic)
2.97
pKa (Strongest Basic)
1.71
PSA
118.81 Å2
Refractivity
134.92 m3·mol-1
Polarizability
45.35 Å3
Rotatable Bond Count
7
H Bond Acceptor Count
7
H Bond Donor Count
2
Physiological Charge
-1
Number of Rings
5
Bioavailability
1
MDDR-Like Rule
true
Dược Lực Học : 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.
Cơ Chế Tác Dụng : 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. 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.
Dược Động Học :
▧ 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.
▧ 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
Độc Tính : 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.
Chỉ Định : 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.
Tương Tác Thuốc :
  • 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
Liều Lượng & Cách Dùng : Tablet - Oral - 16 mg
Tablet - Oral - 32 mg
Tablet - Oral - 4 mg
Tablet - Oral - 8 mg
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Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00796
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=2541
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508342
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07468
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00626
ChemSpider
http://www.chemspider.com/Chemical-Structure.2445.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50240609
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0186-0004-31
PharmGKB
http://www.pharmgkb.org/drug/PA448765
Wikipedia
http://en.wikipedia.org/wiki/Candesartan
RxList
http://www.rxlist.com/cgi/generic/candesar.htm
Drugs.com
http://www.drugs.com/cdi/candesartan.html
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