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
SMILES
Cl.CCCCC1=NC2(CCCC2)C(=O)N1CC3=CC=C(C=C3)C4=CC=CC=C4C5=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
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.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
| 1.1 nM [Ki] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | AVAPRO Approved UseAVAPRO 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 Date1997 |
|||
| Primary | AVAPRO Approved UseAVAPRO 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 Date1997 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
|
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 |
|
4.9 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 |
|
5.3 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 |
|
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 |
|
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 |
|
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 |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
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 |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
10% |
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: |
healthy, 20-45 |
|
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: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Disorder fetal... AEs leading to discontinuation/dose reduction: Disorder fetal Sources: |
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: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Hyperkalemia... AEs leading to discontinuation/dose reduction: Hyperkalemia (2.1%) Sources: |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Disorder fetal | 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: |
unhealthy Health Status: unhealthy Sources: |
| 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: |
unhealthy Health Status: unhealthy Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: - |
no [IC50 224 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: - |
no [IC50 483 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: - |
no [IC50 >1000 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: - |
no [IC50 >1000 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: - |
no [IC50 >1000 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/20222053/ Page: - |
no | |||
Page: 13.0 |
no | |||
Page: 13.0 |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/20222053/ Page: - |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/20222053/ Page: - |
weak | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: - |
yes [IC50 172 uM] | |||
Sources: https://jpet.aspetjournals.org/content/304/2/862 Page: - |
yes [IC50 7.2 uM] |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Page: 12.0 |
yes | |||
Page: 12.0 |
yes | yes (co-administration study) Comment: in clinical studies the consequences of concomitant irbesartan on the pharmacodynamics of warfarin were negligible Page: 12.0 |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Sources: https://jpet.aspetjournals.org/content/304/2/862 Page: - |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Irbesartan slows the development of diabetic nephropathy by up to 70% in hypertensive diabetic patients. | 2002-01-05 |
|
| Irbesartan prevents the progression of kidney disease or death in patients with type 2 diabetes and high blood pressure. | 2002-01-05 |
|
| Vasoconstriction is determined by interstitial rather than circulating angiotensin II. | 2002-01 |
|
| Angiotensin peptides modulate bradykinin levels in the interstitium of the dog heart in vivo. | 2002-01 |
|
| The protective effect of blocking angiotensin in both type I and type II diabetics with nephropathy. | 2001-12 |
|
| AT(2) receptor-mediated vasodilation in the heart: effect of myocardial infarction. | 2001-12 |
|
| Irbesartan, an angiotensin type 1 receptor inhibitor, regulates the vascular oxidative state in patients with coronary artery disease. | 2001-11-15 |
|
| Drug companies should not have the final say in the design of clinical trials. | 2001-11 |
|
| Influence of irbesartan and enalapril on changes of renal function associated with the established phase of l-NAME hypertension. | 2001-11 |
|
| Renal protection by angiotensin II receptor antagonists in patients with type 2 diabetes. | 2001-10-15 |
|
| Vasoconstrictor effect of the angiotensin-converting enzyme-resistant, chymase-specific substrate [Pro(11)(D)-Ala(12)] angiotensin I in human dorsal hand veins: in vivo demonstration of non-ace production of angiotensin II in humans. | 2001-10-09 |
|
| Comparative efficacy of olmesartan, losartan, valsartan, and irbesartan in the control of essential hypertension. | 2001-10-06 |
|
| [Irbesartan in hypertension. A plus for therapy compliance]. | 2001-10-04 |
|
| [Effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes]. | 2001-10-01 |
|
| [Clinical study of the month. Nephroprotective role of angiotensin II receptor antagonists in type 2 diabetes: results of the IDNT and RENAAL trials]. | 2001-10 |
|
| Selective angiotensin II receptor antagonism reduces insulin resistance in obese Zucker rats. | 2001-10 |
|
| Relation between clinical and therapeutic variables and quality of life in hypertension. | 2001-10 |
|
| Comparative effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia and gout. | 2001-10 |
|
| Treatment with irbesartan or atenolol improves endothelial function in essential hypertension. | 2001-10 |
|
| Angiotensin converting enzyme gene polymorphism predicts blood pressure response to angiotensin II receptor type 1 antagonist treatment in hypertensive patients. | 2001-10 |
|
| A clinical trial in type 2 diabetic nephropathy. | 2001-10 |
|
| Angiotensin II receptor blockers and nephropathy trials. | 2001-10 |
|
| pK(a) determination of angiotensin II receptor antagonists (ARA II) by spectrofluorimetry. | 2001-10 |
|
| The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. | 2001-09-20 |
|
| Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. | 2001-09-20 |
|
| Impact of the renin-angiotensin system on cerebral perfusion following subarachnoid haemorrhage in the rat. | 2001-09-01 |
|
| Adenovirus-mediated overexpression and stimulation of the human angiotensin II type 2 receptor in porcine cardiac fibroblasts does not modulate proliferation, collagen I mRNA expression and ERK1/ERK2 activity, but inhibits protein tyrosine phosphatases. | 2001-09 |
|
| Effect of angiotensin II type 1 receptor blockade on experimental hepatic fibrogenesis. | 2001-09 |
|
| Differentiation in the angiotensin II receptor 1 blocker class on autonomic function. | 2001-09 |
|
| Angiotensin II-induced apoptosis in rat cardiomyocyte culture: a possible role of AT1 and AT2 receptors. | 2001-09 |
|
| The pharmacokinetics and pharmacodynamics of irbesartan in heart failure. | 2001-09 |
|
| Irbesartan effects on renal function in patients with renal impairment and hypertension: a drug-withdrawal study. | 2001-09 |
|
| Angiotensin AT1 receptor antagonist irbesartan decreases lesion size, chemokine expression, and macrophage accumulation in apolipoprotein E-deficient mice. | 2001-09 |
|
| [Effects of inhibitors of angiotensin-converting enzyme combined with antagonists of angiotensin II receptors on endothelial function in patients with chronic cardiac insufficiency]. | 2001-08-25 |
|
| New stuff about the diabetic kidney. | 2001-08-11 |
|
| [Treatment of hypertension in patients with type 2 diabetes. Sartan also protects the kidneys]. | 2001-08-09 |
|
| Acute oliguric renal failure associated with angiotensin II receptor antagonists. | 2001-08 |
|
| Hemodynamic effects of the angiotensin II receptor antagonist irbesartan in patients with cirrhosis and portal hypertension. | 2001-08 |
|
| Irbesartan achieves consistent and effective use over 1 year. | 2001-07-28 |
|
| [Angiotensin II receptor antagonists: different or equivalent?]. | 2001-07-27 |
|
| Irbesartan normalises the deficiency in glomerular nephrin expression in a model of diabetes and hypertension. | 2001-07 |
|
| Different types of antagonism by losartan and irbesartan on the effects of angiotensin II and its degradation products in rabbit arteries. | 2001-04 |
|
| Pharmacology of AT1-receptor blockers. | 2001 |
|
| The relationship between dose and antihypertensive effect for different AT1-receptor blockers. | 2001 |
|
| Clinical comparative trials of angiotensin II type 1 (AT1)-receptor blockers. | 2001 |
|
| [Current treatment of diabetic nephropathy in patients with type II diabetes mellitus. Most recent progress]. | 2001 |
|
| Drug interactions with irbesartan. | 2001 |
|
| [Choosing the dose of aprovel (irbesartan) in patients with chronic heart insufficiency]. | 2001 |
|
| Hypertension and diabetes: the scope of the problem. | 2001 |
|
| Clinical differences among angiotensin II receptor antagonists. | 2001 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/irbesartan.html
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12548077
Curator's Comment: Contraction responses to increasing concentrations of Ang I (1 nM-1 uM) were evaluated in organ baths in the presence of captopril (10 uM-1 mM) with or without a chymase inhibitor (1 uM soybean trypsin inhibitor), or irbesartan (0.1 nM-uM), in internal mammary arteries from 25 patients undergoing coronary bypass surgery.
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)
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100000090854
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DTXSID30186568
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DBSALT002632
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3OGC31WUMZ
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ACTIVE MOIETY
SUBSTANCE RECORD