DT-Web

DB08822 - Azilsartan medoxomil


Identification
Name Azilsartan medoxomil
Accession Number DB08822
Type small molecule
Description Azilsartan medoxomil is an angiotensin II receptor antagonist indicated for the treatment of mild to moderate essential hypertension. Azilsartan medoxomil is a prodrug of Azilsartan marketed as "Edarbi" by Takeda. Azilsartan medoxomil has so far been shown to be superior to olmesartan and valsartan in lowering blood pressure.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 568.5336
Groups approved
Monoisotopic Weight 568.159413764
Pharmacology
Indication Treatment of hypertension (alone or as an adjunct).
Mechanism of action Azilsartan medoxomil blocks the angiotensin II type 1 receptor preventing angiotensin II from binding and causing vasoconstriction. Azilsartan's ability to remain tightly bound to AT1 receptors for very long periods after drug washout is among its most unusual features.
Absorption Azilsartan medoxomil is hydrolyzed to the active metabolite azilsartan in the GI tract. The presence of food does not affect oral absorption of azilsartan medoxomil, and the bioavailability is 60% for azilsartan. Maximum plasma concentrations are reached in 1.5 to 3 hours.
Protein binding Azilsartan medoxomil is 99% plasma protein bound.
Biotransformation Azilsartan is metabolized by CYP2C9. CYP2C9 carries out decarboxylation of azilsartan to M-I, and O-dealkylation of azilsartan to M-II. Both M-I and M-II have no pharmacologic activity.
Route of elimination Renal clearance is 2.3 L/minute.
Toxicity Hypotension and diarrhea are most common.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Acetylsalicylic acid Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Aliskiren Azilsartan medoxomil used in combination with aliskiren may lead to hyperkalemia, hypotension, and nephrotoxicity.
Amifostine Azilsartan medoxomil used in combintation with amifostine may lead to hypotension.
Avanafil Pharmacodynamic synergist- increases effects.
Benazepril Pharmacodynamic synergism: dual blockade of renin-angiotensin system. Increases risks of hypotension, hyperkalemia, renal impairment.
Captopril Pharmacodynamic synergism: dual blockade of renin-angiotensin system. Increases risks of hypotension, hyperkalemia, renal impairment.
Celecoxib Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Citric Acid Increases serum potassium.
Diclofenac Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Diflunisal Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Enalapril Pharmacodynamic synergism: dual blockade of renin-angiotensin system. Increases risks of hypotension, hyperkalemia, renal impairment.
Etodolac Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Exenatide Pharmacodynamic synergist- increases effects. May also increase hypoglycemic effects by improving insulin sensitivity.
Fenoprofen Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Flurbiprofen Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Fosinopril Pharmacodynamic synergism: dual blockade of renin-angiotensin system. Increases risks of hypotension, hyperkalemia, renal impairment.
Ibuprofen Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Indomethacin Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Ketoprofen Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Ketorolac Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Liraglutide Pharmacodynamic synergist- increases effects. May also increase hypoglycemic effects by improving insulin sensitivity.
Lisinopril Pharmacodynamic synergism: dual blockade of renin-angiotensin system. Increases risks of hypotension, hyperkalemia, renal impairment.
Lithium Azilsartan medoxomil may increase lithium serum concentrations.
Maraviroc Pharmacodynamic synergist- increases effects.
Meclofenamic acid Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Mefenamic acid Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Meloxicam Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Moexipril Pharmacodynamic synergism: dual blockade of renin-angiotensin system. Increases risks of hypotension, hyperkalemia, renal impairment.
Nabumetone Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Naproxen Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Nitroglycerin Pharmacodynamic synergist- increases effects.
Oxaprozin Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Perindopril Pharmacodynamic synergism: dual blockade of renin-angiotensin system. Increases risks of hypotension, hyperkalemia, renal impairment.
Piroxicam Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Quinapril Pharmacodynamic synergism: dual blockade of renin-angiotensin system. Increases risks of hypotension, hyperkalemia, renal impairment.
Ramipril Pharmacodynamic synergism: dual blockade of renin-angiotensin system. Increases risks of hypotension, hyperkalemia, renal impairment.
Rituximab Azilsartan medoxomil used in combination with rituximab may lead to hypotension.
Sulfasalazine Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Sulindac Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Tadalafil Pharmacodynamic synergist- increases effects.
Tolmetin Increases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
Trandolapril Pharmacodynamic synergism: dual blockade of renin-angiotensin system. Increases risks of hypotension, hyperkalemia, renal impairment.
Food Interactions
  • Food does not affect absorption or bioavailibity.
  • Nutrition/Herbal interaction

Targets


Type-1 angiotensin II receptor
Name Type-1 angiotensin II receptor
Gene Name AGTR1
Pharmacological action yes
Actions antagonist
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Miura SI, Matsuo Y, Nakayama A, Tomita S, Suematsu Y, Saku K: Ability of the new AT1 receptor blocker azilsartan to block angiotensin II-induced AT1 receptor activation after wash-out. J Renin Angiotensin Aldosterone Syst. 2013 Apr 5. - Pubmed
DTHybrid score 0.6666

Predictions


Id Partner name Gene Name Score
5852 Type-2 angiotensin II receptor AGTR2 0.0627
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0503
4757 Cytochrome P450 2C9 CYP2C9 0.0459
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.037
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0321
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0313
4512 Cytochrome P450 3A4 CYP3A4 0.0233
1588 Multidrug resistance protein 1 ABCB1 0.0206
4924 Cytochrome P450 2C8 CYP2C8 0.0195
20 Prostaglandin G/H synthase 1 PTGS1 0.0182
587 Serum albumin ALB 0.0162
1629 Transcription factor AP-1 JUN 0.0146
6179 UDP-glucuronosyltransferase 2B17 UGT2B17 0.0133
238 Peroxisome proliferator-activated receptor gamma PPARG 0.0132
6016 Cytochrome P450 2C19 CYP2C19 0.0128
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.011
4200 Cytochrome P450 1A2 CYP1A2 0.0096
6177 UDP-glucuronosyltransferase 1-10 UGT1A10 0.0077
4119 Cytochrome P450 2D6 CYP2D6 0.0057
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0055
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0053
1729 Solute carrier family 22 member 6 SLC22A6 0.0041
4118 Cytochrome P450 3A5 CYP3A5 0.0038
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