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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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1g |
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Other Sizes |
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Purity: ≥98%
Azilsartan Medoxomil (formerly also known as TAK-491), the ester prodrug of Azilsartan (TAK-536), is a potent and orally bioavailable angiotensin II type 1 (AT1) receptor antagonist, inhibits the RAAS, with an IC50 of 2.6 nM. It is used for the treatment of hypertension. Azilsartan lowers blood pressure by blocking the action of angiotensin II. Azilsartan also inhibits the accumulation of AII-induced inositol 1-phosphate (IP1) in the cell-based assay with an IC50 value of 9.2 nM. Azilsartan medoxomil is a useful and attractive new option for lowering BP in patients with essential hypertension, particularly for those not able to tolerate other antihypertensive drugs.
ln Vitro |
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ln Vivo |
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Animal Protocol |
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ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
During absorption, azilsartan medoxomil is hydrolyzed to azilsartan. The parent drug is not detectable in plasma after oral administration. The absolute bioavailability of azilsartan is estimated to be 60%. Tmax ranges from 1.5 to three hours. Steady-state levels of azilsartan are achieved within five days, and no accumulation in plasma occurs with repeated once-daily dosing. Following oral administration of 14C-labeled azilsartan medoxomil, approximately 55% of radioactivity was recovered in feces and approximately 42% in urine. Of the recovered dose in urine, about 15% was excreted as azilsartan. The volume of distribution of azilsartan is approximately 16 L. In rats, a minimal amount of radiolabelled drug crossed the blood-brain barrier. Azilsartan crossed the placental barrier in pregnant rats and was distributed to the fetus. Renal clearance of azilsartan is approximately 2.3 mL/min. Metabolism / Metabolites After azilsartan medoxomil is hydrolyzed into its active metabolite, azilsartan is metabolized to two primary metabolites, which are pharmacologically inactive. The major metabolite in plasma is metabolite M-II, which is formed via O-dealkylation mediated by CYP2C9. The minor metabolite is metabolite M-I, which is formed via decarboxylation mediated by CYP2C8 and CYP2B6. MII has approximately 50% systemic exposure of azilsartan, and MI has less than 1% systemic exposure of azilsartan. Biological Half-Life The elimination half-life of azilsartan is approximately 11 hours. |
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Toxicity/Toxicokinetics |
Protein Binding
Azilsartan is >99% bound to human plasma proteins, mainly serum albumin. Protein binding is constant at azilsartan plasma concentrations well above the range achieved with recommended doses. |
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References |
J Pharmacol Exp Ther.2011 Mar;336(3):801-8;Am J Hypertens.2007 May;20(5):579-86.
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Additional Infomation |
Pharmacodynamics
Pharmacodynamic effects of azilsartan medoxomil are mediated by its active metabolite, azilsartan. Azilsartan inhibits the pressor effects of an angiotensin II infusion in a dose-related manner. At a single 32 mg dose, azilsartan inhibited the maximal pressor effect by approximately 90% at peak plasma concentrations and by 60% at 24 hours after administration. In healthy subjects receiving single and repeated doses of azilsartan medoxomil, plasma angiotensin I and II concentrations and plasma renin activity increased, while plasma aldosterone concentrations decreased. Like other ARBs, azilsartan causes dose-dependent decrease in peripheral resistance and decreases smooth muscle vascular tone. As azilsartan blocks the angiotensin II receptor, the negative regulatory feedback of angiotensin II on renin secretion is inhibited; however, the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the blood pressure-lowering effect of azilsartan. Blood pressure-lowering effects of antihypertensive agents can be reduced in patients of African descent. However, there are no recommended dosage adjustment of azilsartan on the basis of a patient’s sex, race, or degree of renal or hepatic impairment. Azilsartan medoxomil has negligible effects on serum potassium or sodium levels. Azilsartan does not affect the biosynthesis of angiotensin II nor bradykinin levels. It also does not bind to any ion channels that are involved in cardiovascular regulation. |
Molecular Formula |
C30H24N4O8
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Molecular Weight |
568.53
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Exact Mass |
568.159
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Elemental Analysis |
C, 63.38; H, 4.26; N, 9.85; O, 22.51
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CAS # |
863031-21-4
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Related CAS # |
Azilsartan;147403-03-0;Azilsartan-d5;1346599-45-8;Azilsartan medoxomil monopotassium;863031-24-7
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PubChem CID |
135409642
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Appearance |
Solid powder
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Density |
1.5±0.1 g/cm3
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Boiling Point |
748.0±70.0 °C at 760 mmHg
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Flash Point |
406.2±35.7 °C
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Vapour Pressure |
0.0±2.5 mmHg at 25°C
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Index of Refraction |
1.680
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LogP |
5.73
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Hydrogen Bond Donor Count |
1
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Hydrogen Bond Acceptor Count |
10
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Rotatable Bond Count |
10
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Heavy Atom Count |
42
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Complexity |
1100
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Defined Atom Stereocenter Count |
0
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SMILES |
O=C1OC(COC(C2C3=C(N=C(N3CC3C=CC(C4C(C5NC(=O)ON=5)=CC=CC=4)=CC=3)OCC)C=CC=2)=O)=C(C)O1
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InChi Key |
QJFSABGVXDWMIW-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C30H24N4O8/c1-3-38-28-31-23-10-6-9-22(27(35)39-16-24-17(2)40-30(37)41-24)25(23)34(28)15-18-11-13-19(14-12-18)20-7-4-5-8-21(20)26-32-29(36)42-33-26/h4-14H,3,15-16H2,1-2H3,(H,32,33,36)
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Chemical Name |
(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-((2-(5-oxo-2,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate
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Synonyms |
TAK-491; TAK 491; TAK491; Azilsartan medoxomil; Azilsartan medoxomil potassium; trade name: Edarbi. Ipreziv.
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.66 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 20.8 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.66 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.7589 mL | 8.7946 mL | 17.5892 mL | |
5 mM | 0.3518 mL | 1.7589 mL | 3.5178 mL | |
10 mM | 0.1759 mL | 0.8795 mL | 1.7589 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.