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Details

Stereochemistry ACHIRAL
Molecular Formula C25H20N4O5
Molecular Weight 456.451
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AZILSARTAN

SMILES

CCOc1nc2cccc(c2n1Cc3ccc(cc3)-c4ccccc4-c5nc(=O)o[nH]5)C(=O)O

InChI

InChIKey=KGSXMPPBFPAXLY-UHFFFAOYSA-N
InChI=1S/C25H20N4O5/c1-2-33-24-26-20-9-5-8-19(23(30)31)21(20)29(24)14-15-10-12-16(13-11-15)17-6-3-4-7-18(17)22-27-25(32)34-28-22/h3-13H,2,14H2,1H3,(H,30,31)(H,27,28,32)

HIDE SMILES / InChI

Molecular Formula C25H20N4O5
Molecular Weight 456.451
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: description was created based on several sources, including https://www.takeda.com/news/2011/20110224_3831.html; https://www.ncbi.nlm.nih.gov/pubmed/?term=22346296

Azilsartan medoxomil (trade name Edarb) is an angiotensin II receptor blocker (ARB) that lowers blood pressure by blocking the action of angiotensin II, a vasopressor hormone. It is indicated for the treatment of hypertension to lower blood pressure which reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. Azilsartan medoxomil may be used either alone or in combination with other antihypertensive agents such as chlorthalidone (CLD). As an ARB, azilsartan medoxomil selectively inhibits angiotensin II from binding to the angiotensin II type-1 receptor (AT1). This receptor inhibition provides the antihypertensive activity of azilsartan medoxomil because it blocks the pressor effects of angiotensin II. Azilsartan medoxomil is a prodrug of azilsartan. It is hydrolyzed to the active moiety, azilsartan, in the gastrointestinal (GI) tract during the absorption phase. Azilsartan medoxomil, in combination with the thiazide-like diuretic chlorthalidone, was more effective in lowering systolic BP than azilsartan plus HCTZ.

CNS Activity

Curator's Comment:: In rats, minimal azilsartan-associated radioactivity crossed the blood-brain barrier.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P30556
Gene ID: 185.0
Gene Symbol: AGTR1
Target Organism: Homo sapiens (Human)
0.62 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
EDARBI

Approved Use

Indicated for the treatment of hypertension to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. Edarbi may be used either alone or in combination with other antihypertensive agents.

Launch Date

1.29859204E12
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5355.71 ng/mL
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered: Chlorthalidone
AZILSARTAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
141.3 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: oral
experiment type: single
co-administered:
AZILSARTAN METABOLITE M-I plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status: Fed
191.3 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
AZILSARTAN METABOLITE M-I plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status: Fed
227.7 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
AZILSARTAN METABOLITE M-II plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status: Fed
179.3 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: oral
experiment type: single
co-administered:
AZILSARTAN METABOLITE M-II plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status: Fed
888.3 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
AZILSARTAN plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status: Fed
831.3 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: oral
experiment type: single
co-administered:
AZILSARTAN plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status: Fed
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
46688.2 ng × h/mL
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered: Chlorthalidone
AZILSARTAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1420.5 ng*h/mL
10 mg single, oral
dose: 10 mg
route of administration: oral
experiment type: single
co-administered:
AZILSARTAN METABOLITE M-I plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status: Fed
1592.7 ng*h/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
AZILSARTAN METABOLITE M-I plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status: Fed
1986.5 ng*h/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
AZILSARTAN METABOLITE M-II plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status: Fed
3526 ng*h/mL
10 mg single, oral
dose: 10 mg
route of administration: oral
experiment type: single
co-administered:
AZILSARTAN METABOLITE M-II plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status: Fed
6350.3 ng*h/mL
5 mg single, oral
dose: 5 mg
route of administration: oral
experiment type: single
co-administered:
AZILSARTAN plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status: Fed
6871.7 ng*h/mL
10 mg single, oral
dose: 10 mg
route of administration: oral
experiment type: single
co-administered:
AZILSARTAN plasma
Homo sapiens
population: unhealthy
age: Children
sex:
food status: Fed
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
12.1 h
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered: Chlorthalidone
AZILSARTAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
80 mg 1 times / day unknown, oral
dose: 80 mg
route of administration: Oral
experiment type: UNKNOWN
co-administered:
AZILSARTAN plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
80 mg 1 times / day multiple, oral (max)
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources: Page: p.187
unhealthy, 50.4+/-10.2
n = 179
Health Status: unhealthy
Condition: Hypertension
Age Group: 50.4+/-10.2
Sex: M+F
Population Size: 179
Sources: Page: p.187
Disc. AE: Dizziness, Fatigue...
AEs leading to
discontinuation/dose reduction:
Dizziness (3.35%)
Fatigue (2.79%)
Sources: Page: p.187
320 mg 1 times / day multiple, oral
Overdose
Dose: 320 mg, 1 times / day
Route: oral
Route: multiple
Dose: 320 mg, 1 times / day
Sources: Page: p.6
healthy
80 mg 1 times / day multiple, oral (max)
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources: Page: p.4
unhealthy
n = 2146
Health Status: unhealthy
Condition: Hypertension
Population Size: 2146
Sources: Page: p.4
Disc. AE: Hypotension orthostatic...
AEs leading to
discontinuation/dose reduction:
Hypotension orthostatic (0.4%)
Sources: Page: p.4
AEs

AEs

AESignificanceDosePopulation
Fatigue 2.79%
Disc. AE
80 mg 1 times / day multiple, oral (max)
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources: Page: p.187
unhealthy, 50.4+/-10.2
n = 179
Health Status: unhealthy
Condition: Hypertension
Age Group: 50.4+/-10.2
Sex: M+F
Population Size: 179
Sources: Page: p.187
Dizziness 3.35%
Disc. AE
80 mg 1 times / day multiple, oral (max)
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources: Page: p.187
unhealthy, 50.4+/-10.2
n = 179
Health Status: unhealthy
Condition: Hypertension
Age Group: 50.4+/-10.2
Sex: M+F
Population Size: 179
Sources: Page: p.187
Hypotension orthostatic 0.4%
Disc. AE
80 mg 1 times / day multiple, oral (max)
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources: Page: p.4
unhealthy
n = 2146
Health Status: unhealthy
Condition: Hypertension
Population Size: 2146
Sources: Page: p.4
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no (co-administration study)
Comment: Human liver microsomes (Phenacetin O-deethylation), Maximum inhibition = 5.1%; Coadministration of Azilsartan medoxomil (80 mg QD for 6 days) did not significantly affect Caffeine (200 mg QD on Day 6, CYP1A2 substrate) AUC and Cmax.
Page: 9, 46-47, (ClinPharm) 15, 17-18, 58-59
no [IC50 >100 uM]
no (co-administration study)
Comment: Human liver microsomes (Paclitaxel 6a-hydroxylation), Maximum inhibition = 10.1%; Pioglitazone does not affect systemic exposure to Azilzartan, and systemic exposure to pioglitazone is not affected by Azilzartan.
Page: 9, 46-47, (ClinPharm) 15, 17-18, 77-78
no [IC50 >100 uM]
no (co-administration study)
Comment: Human liver microsomes (Diclofenac 4'-hydroxylation), Inhibited CYP2C9 activities at 30 (14.4%) and 100 mcM (37.9%); Human CYP expressing microsomes derived from B-lymphoblastoid cells (tolbutamide hydroxylation); Coadministration of Azilsartan medoxomil (80 mg QD for 6 days) did not significantly affect Tolbutamide (500 mg QD on Day 6, CYP2C9 substrate) AUC and Cmax.; Azilzartan dose not affect the pharmacokinetics and pharmacodynamics of warfarin and is not expected to significantly affect systemic exposure to other CYP 2C9 substartes.
Page: 9, 46-47, (ClinPharm) 15, 17-18, 58-59, 66-68
no [IC50 >100 uM]
no (co-administration study)
Comment: Human liver microsomes (Bufuralol 1'-hydroxylation), Maximum inhibition = 5.1%; Coadministration of Azilsartan medoxomil (80 mg QD for 6 days) did not significantly affect Dextromethorphan (30 mg QD on Day 6, CYP2D6 substrate) AUC and Cmax.
Page: 9, 46-47, (ClinPharm) 15, 17-18, 58-59
no [IC50 >100 uM]
no (co-administration study)
Comment: Human liver microsomes (Midazolam 17-hydroxylation, Testosterone 6b-hydroxylation), Maximum inhibition = /<0%; Coadministration of Azilsartan medoxomil(80 mg QD for 6 days) did not significantly affect Midazolam (4 mg QD on Day 6, CYP3A4 substrate) AUC and Cmax.; Amlodipine does not affect systemic exposure to Azilzartan, and systemic exposure to amlodipine is not affected by Azilzartan.
Page: 9, 46-47, (ClinPharm) 15, 17-18, 58-59, 73-74
unlikely
unlikely
weak (co-administration study)
Comment: Caco-2 cells (After incubation at 37°C for 2 hours with Azilzartan (at 0, 20, 100, and 500 μmol/L), efflux ratios of digoxin were 6.4, 7.0, 6.6, and 7.23. These results show that Azilsartan had no inhibitory effect on P-gp-mediated efflux activity.; Coadministration of Azilsartan medoxomil (80 mg QD for 6 days) did not significantly affect Fexofenadine (60 mg QD on Day 6, P-gp substrate) AUC and Cmax.; Coadminitration of Azilzartan (80 mg QD for 10 days) increased Digoxin (200 mcg QD for 10 days) AUC0-tau by 2.87% and decreased Cmax by 5.71%.
Page: 35, (ClinPharm) 22-23, 58-59, 62-63
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
inconclusive
major
yes (co-administration study)
Comment: O-dealkylation to form Azilsartan M-II primarily by CYP2C9, Incubation of 14C-AZILSARTAN with microsomes from baculovirus-infected insect cellsexpressuing human CYP isoforms (elimination and formation (M-1 & M-II) rate); Human liver microsomes (16 donors); Clearance of Azilzartan (40 mg QD on Days 1 & 10) is reduced when co-administered with fluconazole (200 mg QD on Days 4-10), a CYP 2C9 inhibitor. This is evident from the ~ 40% increase in AUC, but only ~ 14% increase in Cmax. However, this is not of clinical significance given the flat D-R relationship for Azilzartan and the absence of serious adverse events.; Systemic exposure to glyburide (5 mg QD on DAy 8) is not affected by Azilzartan (40 mg QD for 8 days).
Page: 9, 45, (ClinPharm) 14, 64-65, 69-70
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes (co-administration study)
Comment: Incubation of 14C-AZILSARTAN with microsomes from baculovirus-infected insect cellsexpressuing human CYP isoforms (elimination and formation (M-1 & M-II) rate); Human liver microsomes (16 donors); When co-administered with ketoconazole (400 mg QD on Days 4-10), Cmax of Azilzartan (40 mg QD on Day 1 & 10) decreased by ~ 30% and AUC by ~ 20%. However, the reason for this is not apparent.
Page: 9, 45, (ClinPharm) 14, 64-65
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
TAK-536, a new AT1 receptor blocker, improves glucose intolerance and adipocyte differentiation.
2007 May
Differential pharmacology and benefit/risk of azilsartan compared to other sartans.
2012
A systematic comparison of the properties of clinically used angiotensin II type 1 receptor antagonists.
2013 Apr
Azilsartan, aliskiren, and combination antihypertensives utilizing renin-angiotensin-aldosterone system antagonists.
2014 Sep-Oct
Patents

Sample Use Guides

For 4 weeks during the run-in period, one tablet of TAK-536CCB (as TAK-536/ amlodipine, 20 mg/5 mg, respectively) will be orally administered once daily, before or after breakfast. For 48 weeks during 52 weeks of the treatment period, one tablet of TAK-536TCH (as TAK-536/ amlodipine/amlodipine, 20 mg/5 mg/12.5 mg, respectively) will be orally administered once daily, before or after breakfast. For the remaining 4 weeks of the treatment period, one tablet each of TAK-536CCB and HCTZ 12.5 mg will be orally administered once daily, before or after breakfast.
Route of Administration: Oral
In Vitro Use Guide
Unknown
Substance Class Chemical
Created
by admin
on Sat Jun 26 09:45:10 UTC 2021
Edited
by admin
on Sat Jun 26 09:45:10 UTC 2021
Record UNII
F9NUX55P23
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AZILSARTAN
INN   MART.   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
AZILSARTAN [MART.]
Common Name English
TAK-536
Code English
AZILSARTAN [MI]
Common Name English
AZILSARTAN [INN]
Common Name English
1H-BENZIMIDAZOLE-7-CARBOXYLIC ACID, 1-((2'-(2,5-DIHYDRO-5-OXO-1,2,4-OXADIAZOL- 3-YL)(1,1'-BIPHENYL)-4-YL)METHYL)-2-ETHOXY-
Common Name English
AZILSARTAN [WHO-DD]
Common Name English
AZILSARTAN [JAN]
Common Name English
2-ETHOXY-1-((2'-(5-OXO-2,5-DIHYDRO-1,2,4-OXADIAZOL-3-YL)BIPHENYL-4-YL)METHYL)-1H-BENZIMIDAZOLE-7-CARBOXYLIC ACID
Systematic Name English
AZILSARTAN [VANDF]
Common Name English
AZILSARTAN [USAN]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175561
Created by admin on Sat Jun 26 09:45:11 UTC 2021 , Edited by admin on Sat Jun 26 09:45:11 UTC 2021
NCI_THESAURUS C66930
Created by admin on Sat Jun 26 09:45:11 UTC 2021 , Edited by admin on Sat Jun 26 09:45:11 UTC 2021
LIVERTOX 82
Created by admin on Sat Jun 26 09:45:11 UTC 2021 , Edited by admin on Sat Jun 26 09:45:11 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL57242
Created by admin on Sat Jun 26 09:45:10 UTC 2021 , Edited by admin on Sat Jun 26 09:45:10 UTC 2021
PRIMARY
MERCK INDEX
M2173
Created by admin on Sat Jun 26 09:45:11 UTC 2021 , Edited by admin on Sat Jun 26 09:45:11 UTC 2021
PRIMARY Merck Index
PUBCHEM
135415867
Created by admin on Sat Jun 26 09:45:11 UTC 2021 , Edited by admin on Sat Jun 26 09:45:11 UTC 2021
PRIMARY
LACTMED
Azilsartan
Created by admin on Sat Jun 26 09:45:11 UTC 2021 , Edited by admin on Sat Jun 26 09:45:11 UTC 2021
PRIMARY
INN
8724
Created by admin on Sat Jun 26 09:45:11 UTC 2021 , Edited by admin on Sat Jun 26 09:45:11 UTC 2021
PRIMARY
NDF-RT
N0000178477
Created by admin on Sat Jun 26 09:45:11 UTC 2021 , Edited by admin on Sat Jun 26 09:45:11 UTC 2021
PRIMARY Decreased Blood Pressure [PE]
CAS
147403-03-0
Created by admin on Sat Jun 26 09:45:10 UTC 2021 , Edited by admin on Sat Jun 26 09:45:10 UTC 2021
PRIMARY
EVMPD
SUB31561
Created by admin on Sat Jun 26 09:45:10 UTC 2021 , Edited by admin on Sat Jun 26 09:45:10 UTC 2021
PRIMARY
EPA CompTox
147403-03-0
Created by admin on Sat Jun 26 09:45:10 UTC 2021 , Edited by admin on Sat Jun 26 09:45:10 UTC 2021
PRIMARY
MESH
C521273
Created by admin on Sat Jun 26 09:45:11 UTC 2021 , Edited by admin on Sat Jun 26 09:45:11 UTC 2021
PRIMARY
RXCUI
1091643
Created by admin on Sat Jun 26 09:45:11 UTC 2021 , Edited by admin on Sat Jun 26 09:45:11 UTC 2021
PRIMARY RxNorm
FDA UNII
F9NUX55P23
Created by admin on Sat Jun 26 09:45:10 UTC 2021 , Edited by admin on Sat Jun 26 09:45:10 UTC 2021
PRIMARY
DRUG BANK
DB08822
Created by admin on Sat Jun 26 09:45:10 UTC 2021 , Edited by admin on Sat Jun 26 09:45:10 UTC 2021
PRIMARY
NDF-RT
N0000180999
Created by admin on Sat Jun 26 09:45:11 UTC 2021 , Edited by admin on Sat Jun 26 09:45:11 UTC 2021
PRIMARY Angiotensin 2 Type 1 Receptor Antagonists [MoA]
NCI_THESAURUS
C75107
Created by admin on Sat Jun 26 09:45:11 UTC 2021 , Edited by admin on Sat Jun 26 09:45:11 UTC 2021
PRIMARY
HSDB
8208
Created by admin on Sat Jun 26 09:45:11 UTC 2021 , Edited by admin on Sat Jun 26 09:45:11 UTC 2021
PRIMARY
WIKIPEDIA
AZILSARTAN
Created by admin on Sat Jun 26 09:45:11 UTC 2021 , Edited by admin on Sat Jun 26 09:45:11 UTC 2021
PRIMARY
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MAJOR
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC