IRBESARTAN HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H28N6O.ClH
Molecular Weight	464.99
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CCCCC1=NC2(CCCC2)C(=O)N1CC3=CC=C(C=C3)C4=C(C=CC=C4)C5=NN=NN5

InChI

InChIKey=ZUYFSRQJPNUOQU-UHFFFAOYSA-N

InChI=1S/C25H28N6O.ClH/c1-2-3-10-22-26-25(15-6-7-16-25)24(32)31(22)17-18-11-13-19(14-12-18)20-8-4-5-9-21(20)23-27-29-30-28-23;/h4-5,8-9,11-14H,2-3,6-7,10,15-17H2,1H3,(H,27,28,29,30);1H

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020757s059s067lbl.pdf | https://www.drugs.com/cdi/irbesartan.html

Irbesartan is an angiotensin receptor blocker (ARB) used mainly for the treatment of hypertension. It was developed by Sanofi Research (now part of Sanofi-Aventis). It is marketed under the trade names Aprovel, Karvea, and Avapro. AVAPRO is an angiotensin II receptor blocker (ARB) indicated for: • Treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. • Treatment of diabetic nephropathy in hypertensive patients with type 2 diabetes, an elevated serum creatinine, and proteinuria. Irbesartan is a specific competitive antagonist of AT1 receptors with a much greater affinity (more than 8500-fold) for the AT1 receptor than for the AT2 receptor and no agonist activity.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Type-1 angiotensin II receptor 40 Target ID: CHEMBL227 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020757s059s067lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/10193788 \| https://www.ncbi.nlm.nih.gov/pubmed/8230127	Antagonist 2778		1.1 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020757s055lbl.pdf	Primary		Approved 8429	AVAPRO Approved Use AVAPRO is an angiotensin II receptor blocker (ARB) indicated for: • Treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. (1.1) • Treatment of diabetic nephropathy in hypertensive patients with type 2 diabetes, an elevated serum creatinine, and proteinuria Launch Date 1997
Diabetic nephropathy 35 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020757s059s067lbl.pdf	Primary		Approved 8429	AVAPRO Approved Use AVAPRO is an angiotensin II receptor blocker (ARB) indicated for: • Treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. (1.1) • Treatment of diabetic nephropathy in hypertensive patients with type 2 diabetes, an elevated serum creatinine, and proteinuria Launch Date 1997

C_max

Value	Dose	Analyte	Population
3.3 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.9 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
4.4 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
4.9 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
5.6 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	900 mg 1 times / day multiple, oral dose: 900 mg route of administration: Oral experiment type: MULTIPLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
5.3 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.04 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.9 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
19.8 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
20 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
31.9 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
32.6 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
34.2 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	900 mg 1 times / day multiple, oral dose: 900 mg route of administration: Oral experiment type: MULTIPLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
44.8 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
9.3 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
9.7 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
11 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
14 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
15 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
14 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
14 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	900 mg 1 times / day multiple, oral dose: 900 mg route of administration: Oral experiment type: MULTIPLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
17 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
11 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
16 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9549663	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	IRBESARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020758s079lbl.pdf	unknown, unknown		IRBESARTAN serum	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
900 mg 1 times / day multiple, oral Highest studied dose Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9549663 Page: p.247, p.250	healthy, 20-45 n = 9 Health Status: healthy Age Group: 20-45 Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/9549663 Page: p.247, p.250	Sources: https://pubmed.ncbi.nlm.nih.gov/9549663 Page: p.247, p.250
300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020757s059s067lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Hypertension\|diabetic nephropathy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020757s059s067lbl.pdf Page: p.1	Disc. AE: Disorder fetal... AEs leading to discontinuation/dose reduction: Disorder fetal Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020757s059s067lbl.pdf Page: p.1
300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020757s059s067lbl.pdf Page: p.6	unhealthy Health Status: unhealthy Condition: Diabetic nephropathy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020757s059s067lbl.pdf Page: p.6	Disc. AE: Hyperkalemia... AEs leading to discontinuation/dose reduction: Hyperkalemia (2.1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020757s059s067lbl.pdf Page: p.6

AEs

AE	Significance	Dose	Population
Disorder fetal	Disc. AE	300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020757s059s067lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Hypertension\|diabetic nephropathy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020757s059s067lbl.pdf Page: p.1
Hyperkalemia	2.1% Disc. AE	300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020757s059s067lbl.pdf Page: p.6	unhealthy Health Status: unhealthy Condition: Diabetic nephropathy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020757s059s067lbl.pdf Page: p.6

Overview

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

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A1 110 CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2E1 882 Kv4.3 16 P-gp 1461 BCRP 699 MRP2 383

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: -	no [IC50 224 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: -	no [IC50 483 uM]
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: -	no [IC50 >1000 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: -	no [IC50 >1000 uM]
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: -	no [IC50 >1000 uM]
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20222053/ Page: -	no
CYP1A1 218	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020757s071lbl.pdf#page=13 Page: 13.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020757s071lbl.pdf#page=13 Page: 13.0	no
MRP2 475	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20222053/ Page: -	no
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20222053/ Page: -	weak
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: -	yes [IC50 172 uM]
Kv4.3 16	inhibitor 3277 Sources: https://jpet.aspetjournals.org/content/304/2/862 Page: -	yes [IC50 7.2 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020757s071lbl.pdf#page=12 Page: 12.0	yes
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020757s071lbl.pdf#page=12 Page: 12.0	yes		yes (co-administration study) Comment: in clinical studies the consequences of concomitant irbesartan on the pharmacodynamics of warfarin were negligible Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020757s071lbl.pdf#page=12 Page: 12.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://jpet.aspetjournals.org/content/304/2/862 Page: -

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5959	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5959
ChemicalBook	CB4454663	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4454663
MolPort	MolPort-003-666-550	https://www.molport.com/shop/molecule-link/MolPort-003-666-550
MolPort	MolPort-006-167-687	https://www.molport.com/shop/molecule-link/MolPort-006-167-687
Selleck Chemicals	Irbesartan(Avapro)	http://www.selleckchem.com/products/Irbesartan(Avapro).html
ZINC	ZINC000003872931	http://zinc15.docking.org/substances/ZINC000003872931
eMolecules	32278040	https://www.emolecules.com/cgi-bin/more?vid=32278040
eMolecules	901986	https://www.emolecules.com/cgi-bin/more?vid=901986

PubMed

Title	Date	PubMed
A study of the efficacy and safety of irbesartan in combination with conventional therapy, including ACE inhibitors, in heart failure. Irbesartan Heart Failure Group.	2000 Jan-Feb	10750252
Clinical comparative trials of angiotensin II type 1 (AT1)-receptor blockers.	2001	11683472
Clinical differences among angiotensin II receptor antagonists.	2001	11465913
Vasoconstrictive drugs increase carbonic anhydrase I in vascular smooth muscle while vasodilating drugs reduce the activity of this isozyme by a direct mechanism of action.	2001	11392054
Angiotensin II AT(1) receptor antagonists and platelet activation.	2001	11369820
Drug interaction: omeprazole and phenprocoumon.	2001	11313000
Differential effects of enalapril and irbesartan in experimental papillary necrosis.	2001	11174005
Hemodynamic effects of the angiotensin II receptor antagonist irbesartan in patients with cirrhosis and portal hypertension.	2001 Aug	11487548
p38 Map kinase regulates vascular smooth muscle cell collagen synthesis by angiotensin II in SHR but not in WKY.	2001 Feb	11230337
Angiotensin II type 1 receptor blockers.	2001 Feb 13	11171802
New stuff about the diabetic kidney.	2001 Jul-Aug	11498657
The angiotensin II AT1 receptor antagonist irbesartan prevents thromboxane A2-induced vasoconstriction in the rat hind-limb vascular bed in vivo.	2001 Mar	11327630
[Milestone studies provide evidence: sartans have a nephroprotective effect. Evidence is clear].	2001 May 31	11460392
Selective angiotensin II receptor antagonism reduces insulin resistance in obese Zucker rats.	2001 Oct	11641303
Relation between clinical and therapeutic variables and quality of life in hypertension.	2001 Oct	11593114
[Effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes].	2001 Oct 1	11601118
[Irbesartan in hypertension. A plus for therapy compliance].	2001 Oct 4	11692850
Angiotensin AT1 receptor antagonist irbesartan decreases lesion size, chemokine expression, and macrophage accumulation in apolipoprotein E-deficient mice.	2001 Sep	11486244
Impact of the renin-angiotensin system on cerebral perfusion following subarachnoid haemorrhage in the rat.	2001 Sep 1	11533142
The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes.	2001 Sep 20	11565519

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Hypertension Initial dose: 150 mg orally once a day Maximum dose: 300 mg orally once a day Usual Adult Dose for Diabetic Nephropathy Target maintenance dose: 300 mg orally once a day Use: Treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria (greater than 300 mg/day) in patients with type 2 diabetes and hypertension.

Route of Administration: Oral

In Vitro Use Guide

0.1 uM irbesartan completely blocked the maximum response to Ang I (from 45.8 +/- 6.7% to 1.9 +/- 1.9%, p < 0.001)

Name

Type

Language

IRBESARTAN HYDROCHLORIDE

Common Name

English

IRBESARTAN HCL

Common Name

English

1,3-DIAZASPIRO(4.4)NON-1-EN-4-ONE, 2-BUTYL-3-((2'-(2H-TETRAZOL-5-YL)(1,1'-BIPHENYL)-4-YL)METHYL)-, HYDROCHLORIDE (1:1)

Systematic Name

English

Irbesartan hydrochloride [WHO-DD]

Common Name

English

IRBESARTAN HYDROCHLORIDE [EMA EPAR]

Common Name

English

Code System Code Type Description

SMS_ID

100000090854