AZILSARTAN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H20N4O5
Molecular Weight	456.4501
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC1=NC2=C(N1CC3=CC=C(C=C3)C4=CC=CC=C4C5=NOC(=O)N5)C(=CC=C2)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

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/200796s006lbl.pdfhttps://www.takeda.com/news/2011/20110322_3837.html
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23487168

TAK-536 (generic name: azilsartan) is an angiotensin II type 1 receptor blocker, discovered by Takeda and its mechanism of action is to lower blood pressure by inhibiting action of a vasopressor hormone Angiotensin II. Angiotensin II type 1 receptor antagonists have become an important drug class in the treatment of hypertension and heart failure. TAK-536 is in phase III clinical trial for treatment hypertension. This drug also known as active metabolite of the prodrug azilsartan medoxomil (also known as azilsartan kamedoxomil), but in some countries azilsartan rather than its prodrug is used for oral treatment.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Type-1 angiotensin II receptor 40 Target ID: P30556 Gene ID: 185.0 Gene Symbol: AGTR1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=22346296	Antagonist 2778		0.62 nM [IC50]
Type-1 angiotensin II receptor 40 Target ID: CHEMBL227 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17485025	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/200796s006lbl.pdf	Primary		Approved 8429	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 2011
Hypertension 567 Sources: https://www.takeda.com/news/2011/20110322_3837.html	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
5355.71 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27514506/	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered: Chlorthalidone	Chlorthalidone	AZILSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
141.3 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02451150	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02451150	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02451150	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02451150	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02451150	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02451150	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

Value	Dose	Co-administered	Analyte	Population
46688.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27514506/	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered: Chlorthalidone	Chlorthalidone	AZILSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1420.5 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02451150	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02451150	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02451150	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02451150	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02451150	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02451150	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
12.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27514506/	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered: Chlorthalidone	Chlorthalidone	AZILSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/200796s012lbl.pdf	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/25619410 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: https://pubmed.ncbi.nlm.nih.gov/25619410 Page: p.187	Disc. AE: Dizziness, Fatigue... AEs leading to discontinuation/dose reduction: Dizziness (3.35%) Fatigue (2.79%) Sources: https://pubmed.ncbi.nlm.nih.gov/25619410 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/200796s000lbl.pdf Page: p.6	healthy Health Status: healthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/200796s000lbl.pdf Page: p.6	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/200796s000lbl.pdf Page: p.6
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/200796s000lbl.pdf Page: p.4	unhealthy n = 2146 Health Status: unhealthy Condition: Hypertension Population Size: 2146 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/200796s000lbl.pdf Page: p.4	Disc. AE: Hypotension orthostatic... AEs leading to discontinuation/dose reduction: Hypotension orthostatic (0.4%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/200796s000lbl.pdf Page: p.4

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/25619410 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: https://pubmed.ncbi.nlm.nih.gov/25619410 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: https://pubmed.ncbi.nlm.nih.gov/25619410 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: https://pubmed.ncbi.nlm.nih.gov/25619410 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/200796s000lbl.pdf Page: p.4	unhealthy n = 2146 Health Status: unhealthy Condition: Hypertension Population Size: 2146 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/200796s000lbl.pdf Page: p.4

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 substrate 1737 inducer 781	inhibitor 1767 substrate 1037	inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP1A1 110 CYP2A6 707 P-gp 1461	CYP2C8 693 CYP1A1 349 CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C19 991 CYP2E1 667 CYP4A11 119 P-gp 1537

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A1 218	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=46, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=15 Page: 9, 46, (ClinPharm) 15	no [IC50 >100 uM]
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=46, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=15 Page: 9, 46, (ClinPharm) 15	no [IC50 >100 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=47, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=15 Page: 9, 46-47, (ClinPharm) 15, 17-18	no [IC50 >100 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=47, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=15 Page: 9, 46-47, (ClinPharm) 15, 17-18	no [IC50 >100 uM]
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=47, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=15 Page: 9, 46-47, (ClinPharm) 15, 17-18	no [IC50 >100 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=47, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=15, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=59 Page: 9, 46-47, (ClinPharm) 15, 17-18, 58-59	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=47, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=15, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=59 Page: 9, 46-47, (ClinPharm) 15, 17-18, 58-59
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=47, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=15, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=78 Page: 9, 46-47, (ClinPharm) 15, 17-18, 77-78	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=47, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=15, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=78 Page: 9, 46-47, (ClinPharm) 15, 17-18, 77-78
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=47, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=15, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=59, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=68 Page: 9, 46-47, (ClinPharm) 15, 17-18, 58-59, 66-68	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=47, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=15, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=59, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=68 Page: 9, 46-47, (ClinPharm) 15, 17-18, 58-59, 66-68
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=47, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=15, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=59 Page: 9, 46-47, (ClinPharm) 15, 17-18, 58-59	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=47, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=15, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=59 Page: 9, 46-47, (ClinPharm) 15, 17-18, 58-59
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=47, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=15, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=59, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=74 Page: 9, 46-47, (ClinPharm) 15, 17-18, 58-59, 73-74	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=47, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=15, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=59, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=74 Page: 9, 46-47, (ClinPharm) 15, 17-18, 58-59, 73-74
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=9, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=16 Page: 9, 45-46, (ClinPharm) 16, 19	unlikely
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=35, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=23, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=59 Page: 35, (ClinPharm) 22-23, 58-59, 62-63	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%. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=35, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=23, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=59 Page: 35, (ClinPharm) 22-23, 58-59, 62-63

Drug as victim

Target	Modality	Activity	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=35 Page: 35.0	inconclusive
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=45, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=14, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=65, , https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=70 Page: 9, 45, (ClinPharm) 14, 64-65, 69-70	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). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=45, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=14, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=65, , https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=70 Page: 9, 45, (ClinPharm) 14, 64-65, 69-70
CYP1A1 349	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=45, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=14 Page: 9, 45, (ClinPharm) 14	yes
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=45, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=14 Page: 9, 45, (ClinPharm) 14	yes
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=45, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=14 Page: 9, 45, (ClinPharm) 14	yes
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=45, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=14 Page: 9, 45, (ClinPharm) 14	yes
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=45, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=14 Page: 9, 45, (ClinPharm) 14	yes
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=45, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=14 Page: 9, 45, (ClinPharm) 14	yes
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=45, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=14 Page: 9, 45, (ClinPharm) 14	yes
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=45, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=14 Page: 9, 45, (ClinPharm) 14	yes
CYP4A11 119	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=14 Page: (ClinPharm) 14	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=45, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=14, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=65 Page: 9, 45, (ClinPharm) 14, 64-65	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=45, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=14, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000ClinPharmR.pdf#page=65 Page: 9, 45, (ClinPharm) 14, 64-65

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200796Orig1s000PharmR.pdf#page=30 Page: 8, 30

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:68850	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:68850
ChemicalBook	CB21090899	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB21090899
MolPort	MolPort-023-219-167	https://www.molport.com/shop/molecule-link/MolPort-023-219-167
MolPort	MolPort-023-220-072	https://www.molport.com/shop/molecule-link/MolPort-023-220-072
Selleck Chemicals	azilsartan-tak-536	http://www.selleckchem.com/products/azilsartan-tak-536.html
ZINC	ZINC000000598390	http://zinc15.docking.org/substances/ZINC000000598390
eMolecules	36762351	https://www.emolecules.com/cgi-bin/more?vid=36762351
eMolecules	36905408	https://www.emolecules.com/cgi-bin/more?vid=36905408

PubMed

Title	Date	PubMed
TAK-536, a new AT1 receptor blocker, improves glucose intolerance and adipocyte differentiation.	2007 May	17485025
Azilsartan Medoxomil (Edarbi): The Eighth Angiotensin II Receptor Blocker.	2011 Oct	22346296
Differential pharmacology and benefit/risk of azilsartan compared to other sartans.	2012	22399858
A systematic comparison of the properties of clinically used angiotensin II type 1 receptor antagonists.	2013 Apr	23487168
Azilsartan, aliskiren, and combination antihypertensives utilizing renin-angiotensin-aldosterone system antagonists.	2014 Sep-Oct	22975662

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose in adults is 80 mg taken orally once daily. Consider a starting dose of 40 mg for patients who are treated with high doses of diuretics.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

AZILSARTAN

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 [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 [WHO-DD]

Common Name

English

AZILSARTAN [USAN]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175561