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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/18 22:23:38」(JST)

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Candesartan (rINN) /ˌkændɨˈsɑrtən/ is an angiotensin II receptor antagonist used mainly for the treatment of hypertension. The prodrug candesartan cilexetil is marketed by AstraZeneca and Takeda Pharmaceuticals, commonly under the trade names Blopress, Atacand, Amias, and Ratacand. It is available in generic form.^[1]

Clinical use

As with other angiotensin II receptor antagonists, candesartan is indicated for the treatment of hypertension. Results from the CHARM study (early 2000s) demonstrated the morbidity and mortality reduction benefits of candesartan therapy in congestive heart failure.^[2] Thus, while ACE inhibitors are still considered first-line therapy in heart failure, candesartan can be used in combination with an ACE to achieve improved mortality and morbidity vs. an ACE alone and additionally is an alternative in patients intolerant of ACE inhibitor therapy.

Prehypertension

In a four-year randomized controlled trial, candesartan was compared to placebo to see whether it could prevent or postpone the development of full-blown hypertension in people with so-called prehypertension. During the first two years of the trial, half of participants were given candesartan, and the others received placebo; candesartan reduced the risk of developing hypertension by nearly two-thirds during this period. In the last two years of the study, all participants were switched to placebo. By the end of the study, candesartan had significantly reduced the risk of hypertension, by more than 15%. Serious side effects were actually more common among participants receiving placebo than in those given candesartan.^[3]

Combination with diuretic

Candesartan is also available in a combination formulation with a low dose thiazide diuretic, invariably hydrochlorothiazide, to achieve an additive antihypertensive effect. Candesartan/hydrochlorothiazide combination preparations are marketed under various trade names including Atacand HCT, Hytacand, Blopress Plus, Advantec and Ratacand Plus.

Candesartan cilexetil

Chemistry and pharmacology

Candesartan is marketed as the cyclohexyl 1-hydroxyethyl carbonate (cilexetil) ester, known as candesartan cilexetil. Candesartan cilexetil is metabolised completely by esterases in the intestinal wall during absorption to the active candesartan moieity.

The use of a prodrug form increases the bioavailability of candesartan. Despite this, absolute bioavailability is relatively poor at 15% (candesartan cilexetil tablets) to 40% (candesartan cilexetil solution). Its IC₅₀ is 15 µg/kg.

References

^ http://www.sandoz.com/cs/www.sandoz.com-v4/assets/media/shared/documents/Candesartan_PR.pdf
^ Pfeffer M, Swedberg K, Granger C, Held P, McMurray J, Michelson E, Olofsson B, Ostergren J, Yusuf S, Pocock S (2003). "Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme". Lancet 362 (9386): 759–66. doi:10.1016/S0140-6736(03)14282-1. PMID 13678868.
^ Julius S, Nesbitt SD, Egan BM et al. (July 2006). "Feasibility of treating prehypertension with an angiotensin-receptor blocker". New England Journal of Medicine 354 (16): 1685–97. doi:10.1056/NEJMoa060838. PMID 16537662.

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English Journal

Telmisartan reduces mortality and left ventricular hypertrophy with sympathoinhibition in rats with hypertension and heart failure.

Kishi T, Hirooka Y, Sunagawa K.Author information Department of Advanced Therapeutics for Cardiovascular Diseases, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.AbstractBACKGROUND: Angiotensin II type 1 receptor (AT1R) blockers have various benefits on hypertension and/or heart failure. We demonstrated that telmisartan (TLM), an AT1R blocker, causes sympathoinhibition by reduction of reactive oxygen species (ROS) in the rostral ventrolateral medulla (RVLM) of stroke-prone spontaneously hypertensive rats (SHRSPs). The aim of this study was to determine whether TLM improves survival in rats with hypertension and heart failure.
American journal of hypertension.Am J Hypertens.2014 Feb;27(2):260-7. doi: 10.1093/ajh/hpt188. Epub 2013 Oct 5.
BACKGROUND: Angiotensin II type 1 receptor (AT1R) blockers have various benefits on hypertension and/or heart failure. We demonstrated that telmisartan (TLM), an AT1R blocker, causes sympathoinhibition by reduction of reactive oxygen species (ROS) in the rostral ventrolateral medulla (RVLM) of strok
PMID 24096926

Azilsartan, an angiotensin II type 1 receptor blocker, restores endothelial function by reducing vascular inflammation and by increasing the phosphorylation ratio Ser1177/Thr497 of endothelial nitric oxide synthase in diabetic mice.

Matsumoto S, Shimabukuro M, Fukuda D, Soeki T, Yamakawa K, Masuzaki H, Sata M.Author information Department of Cardio-Diabetes Medicine, The University of Tokushima Graduate School of Health Biosciences, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. mshimabukuro-ur@umin.ac.jp.AbstractBACKGROUND: Azilsartan, an angiotensin II type 1 (AT1) receptor blocker (ARB), has a higher affinity for and slower dissociation from AT1 receptors and shows stronger inverse agonism compared to other ARBs. Possible benefits of azilsartan in diabetic vascular dysfunction have not been established.
Cardiovascular diabetology.Cardiovasc Diabetol.2014 Jan 31;13(1):30. doi: 10.1186/1475-2840-13-30.
BACKGROUND: Azilsartan, an angiotensin II type 1 (AT1) receptor blocker (ARB), has a higher affinity for and slower dissociation from AT1 receptors and shows stronger inverse agonism compared to other ARBs. Possible benefits of azilsartan in diabetic vascular dysfunction have not been established.ME
PMID 24485356

Candesartan Cilexetil 32 mg/Hydrochlorothiazide 25 mg in Unselected Patients with High or Very High Cardiovascular Risk: Efficacy, Safety, and Metabolic Impact.

Bramlage P, Buhck H, Zemmrich C.Author information Institut für Pharmakologie und präventive Medizin, Menzelstrasse 21, 15831, Mahlow, Germany, peter.bramlage@ippmed.de.AbstractBACKGROUND AND OBJECTIVES: Safety and efficacy of the fixed-dose combination candesartan cilexetil 32 mg/hydrochlorothiazide 25 mg has been demonstrated in a number of randomized clinical trials. Because stringent inclusion and exclusion criteria prohibit many high-risk patients from being investigated in clinical trials we aimed to assess the effectiveness, tolerability, and safety in a large unselected cohort of high-risk patients in primary care. The primary objective was the efficacy of candesartan cilexetil 32 mg/hydrochlorothiazide 25 mg in lowering the office-based blood pressure (BP). Secondary objectives were changes of metabolic parameters and safety.
Clinical drug investigation.Clin Drug Investig.2014 Jan 31. [Epub ahead of print]
BACKGROUND AND OBJECTIVES: Safety and efficacy of the fixed-dose combination candesartan cilexetil 32 mg/hydrochlorothiazide 25 mg has been demonstrated in a number of randomized clinical trials. Because stringent inclusion and exclusion criteria prohibit many high-risk patients from being investi
PMID 24482018

Japanese Journal

Novel and practical synthesis of candesartan cilexetil

Heterocycles 81(6), 1503-1508, 2010-06-01
NAID 40017114216

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★リンクテーブル★

リンク元

「カンデサルタン」

Candesartan
Systematic (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
Clinical data
Trade names	Atacand
AHFS/Drugs.com	monograph
MedlinePlus	a601033
Pregnancy; category	AU: D;
Legal status	℞ (Prescription only);
Routes of; administration	oral
Pharmacokinetic data
Bioavailability	15% (candesartan cilexetil)
Metabolism	Candesartan cilexetil: intestinal wall; candesartan: hepatic (CYP2C9)
Biological half-life	9 hours
Excretion	Renal 33%, faecal 67%
Identifiers
CAS Registry Number	139481-59-7
ATC code	C09CA06
PubChem	CID: 2541
IUPHAR/BPS	587
DrugBank	DB00796
ChemSpider	2445
UNII	S8Q36MD2XX
KEGG	D00626
ChEBI	CHEBI:3347
ChEMBL	CHEMBL1016
Chemical data
Formula	C24H20N6O3
Molecular mass	440.45 g/mol
	SMILES O=C(O)c1cccc2nc(OCC)n(c12)Cc5ccc(c3ccccc3c4nnnn4)cc5 ;
	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) ; Key:HTQMVQVXFRQIKW-UHFFFAOYSA-N ;
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　　[★]

英: candesartan
化: カンデサルタンシレキセチル candesartan cilexetil
商: ブロプレス、エカード配合、ユニシア配合、Atacand
関: アンジオテンシンII受容体拮抗薬

降圧薬、アンジオテンシンAT1拮抗プロドラッグ

[1] ttp://www.sandoz.com/cs/www.sandoz.com-v4/assets/media/shared/documents/Candesartan_PR.pdf

[Pfeffer2003-2] Pfeffer M, Swedberg K, Granger C, Held P, McMurray J, Michelson E, Olofsson B, Ostergren J, Yusuf S, Pocock S (2003). "Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme". Lancet 362 (9386): 759–66. doi:10.1016/S0140-6736(03)14282-1. PMID 13678868.

[3] Julius S, Nesbitt SD, Egan BM et al. (July 2006). "Feasibility of treating prehypertension with an angiotensin-receptor blocker". New England Journal of Medicine 354 (16): 1685–97. doi:10.1056/NEJMoa060838. PMID 16537662.

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Atacand