Candesartan improves the functional markers in a dose-dependent manner and also upregulates Ang (1-7), ACE2 and mas1 in the myocardium of DCM rats. Candesartan reduces various ER stress and apoptosis markers and the number apoptotic cells in the Candesartan treated rats. Candesartan cilexetil shows angiotensin-II blocking action in a dose-dependent manner in rats with dilated cardiomyopathy. Candesartan cilexetil reduces the left ventricular end-diastolic pressure and heart weight/body weight ratio, the area of myocardial fibrosis and expressions of transforming growth factor-beta1 and collagen-III mRNA. Candesartan cilexetil (1 mg/kg, p.o.) and enalapril (10 mg/kg, p.o.) reduces blood pressure to the same extent 5 hours after administration on the 1st and the 7th day. Candesartan cilexetil significantly increases renal blood flow without any changes in the cardiac index. TCV-116 and enalapril also tends to increase splanchnic blood flow following the 1st dose but not the 7th dose. Candesartan cilexetil is absorbed from the small intestine and hydrolyzed completely to the pharmacologically active metabolite M-I during absorption process.

Absorption, Distribution and Excretion
Following administration of the candesartan cilexetil prodrug, the absolute bioavailability of candesartan cilexetil is estimated to be 15%. High-fat diets have no effect on the bioavailability of candesartan cilexetil. Approximately 26% of the oral dose of candesartan cilexetil is excreted unchanged in the urine. Candesartan is primarily excreted unchanged in the urine and feces (via bile). 0.13 L/kg 0.37 mL/min/kg hr Metabolism/Metabolites The prodrug candesartan cilexetil is rapidly and completely esterified in the intestinal wall to produce the active drug, candesartan. Candesartan is primarily excreted unchanged in the urine and via the bile route in the feces. A small amount of hepatic metabolism of candesartan (<20%) occurs via O-deethylation at cytochrome P450 2C9, producing an inactive metabolite. Candesartan undergoes N-glucuronidation of the tetrazolium ring via uridine diphosphate glucuronyl transferase 1A3 (UGT1A3). O-glucuronidation may also occur. 75% of candesartan is excreted unchanged in urine and feces.

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Biological half-life
Approximately 9 hours.

Protein Binding
Candesartan has a high binding rate to plasma proteins (>99%) and cannot 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 medoxomil belongs to the biphenyl class of compounds. Candesartan is an angiotensin receptor blocker (ARB) that can be used alone or in combination with other drugs to treat hypertension. It is taken orally as a prodrug, candesartan medoxomil, and is rapidly converted to its active metabolite, candesartan, during gastrointestinal absorption. Candesartan lowers blood pressure by antagonizing the renin-angiotensin-aldosterone system (RAAS); it competitively binds to the type 1 angiotensin II receptor (AT1) subtype with angiotensin II, thereby blocking the pressor effect of angiotensin II. Unlike angiotensin-converting enzyme (ACE) inhibitors, ARBs do not cause adverse reactions such as dry cough. Candesartan can be used to treat hypertension, isolated systolic hypertension, left ventricular hypertrophy, and diabetic nephropathy. It can also be used as an alternative treatment for heart failure, systolic dysfunction, myocardial infarction, and coronary artery disease. Candesartan medoxomil is a synthetic benzimidazole angiotensin II receptor antagonist prodrug with antihypertensive activity. Candesartan medoxomil is hydrolyzed to candesartan during gastrointestinal absorption. It selectively competes with angiotensin II for binding to angiotensin II receptor type 1 (AT1) in vascular smooth muscle, thereby blocking angiotensin II-mediated vasoconstriction and inducing vasodilation. Furthermore, antagonism of AT1 in the adrenal glands inhibits angiotensin II-stimulated aldosterone synthesis and secretion from the adrenal cortex; sodium and water excretion increases, followed by a decrease in plasma volume and blood pressure. See also: candesartan (containing the active ingredient); candesartan medoxomil; hydrochlorothiazide (one of the components). Drug Indications Candesartan can be used as a first-line drug for the treatment of isolated hypertension, isolated systolic hypertension, and left ventricular hypertrophy. It can also be used as a first-line drug to slow the progression of diabetic nephropathy. Candesartan can also be used as a second-line drug for the treatment of patients with congestive heart failure, systolic dysfunction, myocardial infarction, and coronary artery disease who are intolerant to ACE inhibitors.
FDA Label
Diabetic Retinopathy, Essential Hypertension, Heart Failure
Diabetic Retinopathy, Essential Hypertension, Heart Failure
Mechanism of Action

Candesartan selectively blocks the binding of angiotensin II to AT1 receptors, acting on multiple tissues including vascular smooth muscle and the adrenal glands. This inhibits the vasoconstriction and aldosterone secretion mediated by angiotensin II via AT1 receptors, resulting in an overall decrease in blood pressure. Candesartan is more than 10,000 times more selective for AT1 receptors than for AT2 receptors. Inhibition of aldosterone secretion increases sodium and water excretion while decreasing potassium excretion.
Pharmacodynamics

Candesartan cilexetil is an angiotensin receptor blocker (ARB) prodrug that is rapidly converted to its active metabolite, candesartan, during gastrointestinal absorption. Candesartan exerts its antihypertensive effect by antagonizing the pressor effect of angiotensin II, thereby acting through the renin-angiotensin-aldosterone system (RAAS). The renal juvenile autoimmune system (RAAS) is a homeostatic mechanism regulating hemodynamics, water, and electrolyte balance. When the sympathetic nervous system is excited or renal blood pressure or blood flow decreases, the granular cells of the juxtaglomerular apparatus release renin. Renin cleaves circulating angiotensinogen into angiotensin I, which is then cleaved into angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II raises blood pressure by increasing peripheral resistance, promoting aldosterone secretion, increasing renal reabsorption of sodium and water, and altering cardiovascular structure. Angiotensin II binds to two receptors: angiotensin II receptor type 1 (AT1) and angiotensin II receptor type 2 (AT2). AT1 is a G protein-coupled receptor (GPCR) that mediates the vasoconstrictive and aldosterone secretion effects of angiotensin II. Recent studies have shown that AT2 antagonizes the effects mediated by AT1 and directly affects long-term blood pressure control by inducing vasodilation and increasing urinary sodium excretion. Angiotensin receptor blockers (ARBs) are non-peptide competitive inhibitors of AT1. ARBs block the vasopressive and cell proliferation-stimulating effects of angiotensin II. Unlike ACE inhibitors, ARBs do not affect bradykinin-induced vasodilation. The overall effect of ARBs is to lower blood pressure.

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

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.09 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (4.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)