体外活性：坎地沙坦阻断血管紧张素 II 对血管紧张素 II 1 型 (AT1) 受体的作用。坎地沙坦西酯是一种前药，在胃肠吸收过程中通过酯水解活化为坎地沙坦。

Candesartan 以剂量依赖性方式改善 DCM 大鼠心肌中的功能标志物，并上调 Ang (1-7)、ACE2 和 mas1。坎地沙坦可降低经坎地沙坦治疗的大鼠的各种内质网应激和细胞凋亡标记物以及凋亡细胞的数量。 Candesartan cilexetil 对扩张型心肌病大鼠显示出剂量依赖性的血管紧张素-II 阻断作用。 Candesartan cilexetil 可降低左心室舒张末压、心脏重量/体重比、心肌纤维化面积以及转化生长因子-β1 和胶原蛋白 III mRNA 的表达。坎地沙坦西酯（1 mg/kg，口服）和依那普利（10 mg/kg，口服）在第 1 天和第 7 天给药后 5 小时，血压降低程度相同。坎地沙坦西酯显着增加肾血流量，而不改变心脏指数。 TCV-116 和依那普利在第 1 次给药后也往往会增加内脏血流量，但在第 7 次给药后则不会。坎地沙坦西酯从小肠吸收，在吸收过程中完全水解为药理活性代谢产物MI。

Absorption, Distribution and Excretion
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 effect on the bioavailability of candesartan from candesartan cilexetil.
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).
0.13 L/kg
0.37 mL/min/kg

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Metabolism / Metabolites
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.

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Biological Half-Life
Approximately 9 hours.

Protein Binding
Candesartan is highly bound to plasma proteins (>99%) and does not penetrate red blood cells.

Am J Health Syst Pharm.2000 Apr 15;57(8):739-46;Toxicology.2012 Jan 27;291(1-3):139-45.

Candesartan cilexetil is a member of biphenyls.
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 Cilexetil is a synthetic, benzimidazole-derived angiotensin II receptor antagonist prodrug with antihypertensive activity. After hydrolysis of candesartan cilexetil to candesartan during gastrointestinal absorption, candesartan selectively competes with angiotensin II for the binding of the angiotensin II receptor subtype 1 (AT1) in vascular smooth muscle, blocking angiotensin II-mediated vasoconstriction and inducing vasodilatation. In addition, antagonism of AT1 in the adrenal gland inhibits angiotensin II-stimulated aldosterone synthesis and secretion by the adrenal cortex; sodium and water excretion increase, followed by a reduction in plasma volume and blood pressure.
See also: Candesartan (has active moiety); Candesartan cilexetil; hydrochlorothiazide (component of).

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Drug 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.
FDA Label
Diabetic retinopathy, Essential hypertension, Heart Failure
Diabetic retinopathy, Essential hypertension, Heart Failure

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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.

C33H34N6O6

610.66

610.253

145040-37-5

Candesartan;139481-59-7;Candesartan-d4;1346604-70-3

2540

White to off-white solid powder

1.4±0.1 g/cm3

843.3±75.0 °C at 760 mmHg

168-170?C

463.8±37.1 °C

0.0±3.1 mmHg at 25°C

1.667

7.79

143.34

1

10

13

45

962

0

GHOSNRCGJFBJIB-UHFFFAOYSA-N

InChI=1S/C33H34N6O6/c1-3-42-32-34-28-15-9-14-27(31(40)43-21(2)44-33(41)45-24-10-5-4-6-11-24)29(28)39(32)20-22-16-18-23(19-17-22)25-12-7-8-13-26(25)30-35-37-38-36-30/h7-9,12-19,21,24H,3-6,10-11,20H2,1-2H3,(H,35,36,37,38)

1-(((cyclohexyloxy)carbonyl)oxy)ethyl 1-((2-(1H-tetrazol-5-yl)-[1,1-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 2.5 mg/mL (4.09 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (4.09 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。