体外活性：坎地沙坦与 CHO-AT1 细胞中的血管紧张素 II AT1 受体高度特异性结合，K−1 为 0.001 min−1。坎地沙坦不会影响细胞活力或增殖，但会增加 KU-19-19 细胞培养基中 VEGF 和 IL-8 的表达。坎地沙坦 (0.1 nM) 可使血管紧张素 II 的最大收缩反应降低约 50%。激酶测定：将细胞铺板于 24 孔板中并培养直至汇合。实验前，室温下用每孔 0.5 mL 的 DMEM 洗涤细胞 3 次。除去培养基后，加入 400 μL 结合 DMEM，然后将板在 37 ℃ 下放置 15 分钟。对于饱和结合测定，将细胞与终体积为 0.5 mL 的逐渐浓度的 [3H]坎地沙坦（终浓度在 0.15 nM 至 15 nM 之间）在 37℃ 下孵育 5 分钟至 180 分钟。对于竞争性结合测定，添加 50 μL 缓冲液或 50 μL 含有浓度不断增加的未标记坎地沙坦的缓冲液。 30分钟后，加入50μL含有[3H]坎地沙坦（终浓度1.1nM）或[3H]坎地沙坦（终浓度1.0nM）的缓冲液，并将细胞在37℃下进一步孵育30分钟。细胞测定：将 KU-19-19 细胞以每孔 2 × 104 的细胞密度接种到 96 孔板中，并使其生长过夜。然后用不同浓度的坎地沙坦处理细胞不同的时间。通过 Alamar Blue 测定法测定细胞活力，以检查坎地沙坦的细胞毒性和抗增殖作用。在酶标仪中测定每个孔的吸光度值。

在降低神经元损伤、病变体积和小胶质细胞活化方面，坎地沙坦（腹腔注射；1 mg/kg/天；持续 1、3 或 28 dpi）具有神经保护作用，保护 CBF 并改善 TBI 动物模型。经营行为[3]。

Animal/Disease Models: C57BL/6 mice (nineweeks old, male, 22–28 g)[3]
Doses: 1 mg/kg
Route of Administration: ip; 1 mg/kg/day; continuously for 1, 3 or 28 dpi.
Experimental Results: decreased the lesion volume after CCI injury by approximately 50%, diminished the number of dying neurons, lessened the number of activated microglial cells, protected cerebral blood flow (CBF), and decreased the expression of the cytokine TGFß1 while increasing expression of TGFB3 . demonstrated good motor skills on the rotarod 3 days after injury, and improved performance in the Morris water maze 4 weeks after injury.

Absorption, Distribution and Excretion
The volume of distribution of candesartan is 0.13 L/kg. Candesartan is highly bound to plasma proteins (>99%) and does not penetrate red blood cells. The protein binding is constant at candesartan plasma concentrations well above the range achieved with recommended doses. In rats, it has been demonstrated that candesartan crosses the blood-brain barrier poorly, if at all. It has also been demonstrated in rats that candesartan passes across the placental barrier and is distributed in the fetus.
Following administration of candesartan cilexetil, the absolute bioavailability of candesartan was estimated to be 15%. After tablet ingestion, the peak serum concentration (Cmax) is reached after 3 to 4 hours. Food with a high fat content does not affect the bioavailability of candesartan after candesartan cilexetil administration.
Total plasma clearance of candesartan is 0.37 mL/min/kg, with a renal clearance of 0.19 mL/min/kg. When candesartan is administered orally, about 26% of the dose is excreted unchanged in urine. Following an oral dose of (14)C-labeled candesartan cilexetil, approximately 33% of radioactivity is recovered in urine and approximately 67% in feces. Following an intravenous dose of (14)C-labeled candesartan, approximately 59% of radioactivity is recovered in urine and approximately 36% in feces. Biliary excretion contributes to the elimination of candesartan.
It is not known whether candesartan is excreted in human milk, but candesartan has been shown to be present in rat milk.

---

Metabolism / Metabolites
Candesartan cilexetil is rapidly and completely bioactivated by ester hydrolysis during absorption from the gastrointestinal tract to candesartan, a selective AT1 subtype angiotensin II receptor antagonist. Candesartan is mainly excreted unchanged in urine and feces (via bile). It undergoes minor hepatic metabolism by O-deethylation to an inactive metabolite.
Candesartan has known human metabolites that include 3-[[4-[2-[2-[(3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxyoxan-2-yl]tetrazol-5-yl]phenyl]phenyl]methyl]-2-ethoxy-1H-benzimidazol-3-ium-4-carboxylic acid and (2S,3S,4S,5R)-6-[2-Ethoxy-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]benzimidazole-4-carbonyl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid.

---

Biological Half-Life
The elimination half-life of candesartan is approximately 9 hours.

Toxicity Summary
IDENTIFICATION AND USE: Candesartan is a white to off white powder that is formulated into oral tablets. Candesartan is an angiotensin II type 1 (AT1) receptor antagonist. It is used alone or in combination with other classes of antihypertensive agents in the management of hypertension in adults and children from 1 to less than 17 years of age. It is also used for the treatment of heart failure in adults with left ventricular systolic dysfunction to reduce cardiovascular death and heart failure hospitalizations. HUMAN EXPOSURE AND TOXICITY: The most likely manifestations of candesartan overdose include hypotension, dizziness, and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. While candesartan can be used in hypertensive children, it is not approved for use in children less one 1 year of age as drugs that act directly on the renin-angiotensin system (RAS) can have effects on the development of immature kidneys. The use of candesartan is also contraindicated during pregnancy. While use during the first trimester does not suggest a risk of major anomalies, use during the second and third trimester may cause teratogenicity and severe fetal and neonatal toxicity. Fetal toxic effects may include anuria, oligohydramnios, fetal hypocalvaria, intrauterine growth restriction, premature birth and patent ductus arteriosus. Stillbirth or neonatal death may occur. Anuria-associated oligohydramnios may produce fetal limb contractures, craniofacial deformation, and pulmonary hypoplasia. Severe anuria and hypotension, resistant to both pressor agents and volume expansion, may occur in the newborn following in utero exposure to candesartan. ANIMAL STUDIES: There was no evidence of carcinogenicity when candesartan was orally administered to mice. Also, the fertility of male and female rats was unaffected by administration of candesartan. No maternal toxicity or adverse effects on fetal development were observed when candesartan was administered to pregnant mice at oral doses up to 1000 mg/kg. However, doses as low as 10 mg/kg/day administered to rats were associated with reduced survival and an increased incidence of hydronephrosis in the offspring. Candesartan given to pregnant rabbits at an oral dose of 3 mg/kg/day caused maternal toxicity (decreased body weight and death) but had no adverse effects on fetal survival, fetal weight, or external, visceral, or skeletal development. Candesartan and its O-deethyl metabolite tested positive for genotoxicity in the in vitro Chinese hamster lung (CHL) chromosomal aberration assay. Neither compound tested positive in the Ames microbial mutagenesis assay or the in vitro mouse lymphoma cell assay. Candesartan (but not its O-deethyl metabolite) was also evaluated in vivo in the mouse micronucleus test and in vitro in the Chinese hamster ovary (CHO) gene mutation assay, in both cases with negative results. Candesartan cilexetil was evaluated in the Ames test, the in vitro mouse lymphoma cell and rat hepatocyte unscheduled DNA synthesis assays and the in vivo mouse micronucleus test, in each case with negative results.

---

Hepatotoxicity
Candesartan has been associated with a low rate of serum aminotransferase elevations (
Likelihood score: C (Probable cause of rare instances of clinically apparent liver injury).

---

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Preliminary evidence suggests that candesartan passes poorly into milk and is barely detectable in the plasma of breastfed infants. Use of candesartan is not a reason to discontinue nursing, but use caution in newborn and preterm infants.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

---

Interactions
Do not co-administer aliskiren with Atacand in patients with diabetes. Avoid use of aliskiren with Atacand in patients with renal impairment (GFR <60 mL/min).
Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors, and with some angiotensin II receptor antagonists. An increase in serum lithium concentration has been reported during concomitant administration of lithium with Atacand. Monitor serum lithium levels.
Patients on diuretics, and especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with Atacand. The possibility of symptomatic hypotension with the use of Atacand can be minimized by discontinuing the diuretic prior to initiation of treatment and/or lowering the initial dose of Atacand. /From table/
Atacand decreases the production of aldosterone. Potassium-sparing diuretics or potassium supplements should be given only for documented hypokalemia and with frequent monitoring of serum potassium. Potassium-containing salt substitute should also be used with caution. /From table/
For more Interactions (Complete) data for CANDESARTAN (8 total), please visit the HSDB record page.

---

Non-Human Toxicity Values
LDDog (male) oral > 2,000 mg/kg
LD50 Rat oral > 2,000 mg/kg
LD50 Mouse oral > 2,000 mg/kg
LD50 Rat (male) iv 1,350 mg/kg
For more Non-Human Toxicity Values (Complete) data for CANDESARTAN (11 total), please visit the HSDB record page.

[1]. 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.

[2]. Chronic peripheral administration of the angiotensin II AT(1) receptor antagonist candesartan blocks brain AT(1) receptors. Brain Res. 2000 Jul 14;871(1):29-38.

[3]. Candesartan, an angiotensin II AT₁-receptor blocker and PPAR-γ agonist, reduces lesion volume and improves motor and memory function after traumatic brain injury in mice. Neuropsychopharmacology. 2012 Dec;37(13):2817-29.

Therapeutic Uses
Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents
Atacand is indicated for the treatment of hypertension in adults and children 1 to < 17 years of age. It may be used alone or in combination with other antihypertensive agents. /Included in US product labeling/
Atacand is indicated for the treatment of heart failure (NYHA class II-IV) in adults with left ventricular systolic dysfunction (ejection fraction = 40%) to reduce cardiovascular death and to reduce heart failure hospitalizations. Atacand also has an added effect on these outcomes when used with an ACE inhibitor. /Included in US product labeling/
Both angiotensin II receptor antagonists and ACE inhibitors have been shown to slow the rate of progression of renal disease in hypertensive patients with diabetes mellitus and microalbuminuria or overt nephropathy, and use of a drug from either class is recommended in such patients. /NOT included in US product label/
For more Therapeutic Uses (Complete) data for CANDESARTAN (7 total), please visit the HSDB record page.

---

Drug Warnings
/BOXED WARNING/ WARNING: FETAL TOXICITY. When pregnancy is detected, discontinue Atacand as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Atacand as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.
Neonates with a history of in utero exposure to Atacand: If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.
FDA Pregnancy Risk Category: D /POSITIVE EVIDENCE OF RISK. Studies in humans, or investigational or post-marketing data, have demonstrated fetal risk. Nevertheless, potential benefits from the use of the drug may outweigh the potential risk. For example, the drug may be acceptable if needed in a life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective./
For more Drug Warnings (Complete) data for CANDESARTAN (19 total), please visit the HSDB record page.

C24H20N6O3

440.45

440.159

139481-59-7

Candesartan Cilexetil;145040-37-5;Candesartan-d4;1346604-70-3;Candesartan-d5;1189650-58-5

2541

White to off-white solid powder

1.4±0.1 g/cm3

754.8±70.0 °C at 760 mmHg

183-185°C

410.3±35.7 °C

0.0±2.7 mmHg at 25°C

1.719

5.01

118.81

2

7

7

33

660

0

HTQMVQVXFRQIKW-UHFFFAOYSA-N

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)

2-ethoxy-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid

CV11974; CV-11974, CV 11974, Trade names: Blopress, Atacand, Amias, and Ratacand

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 (5.68 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。

---

配方 2 中的溶解度: ≥ 2.5 mg/mL (5.68 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 储备液添加到 900 μL 玉米油中并混合均匀。

---

View More

配方 3 中的溶解度: 30%Propylene glycol, 5%Tween 80, 65% D5W:30 mg/mL

---

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。