Irbesartan

Synonyms :
2-Butyl-3-{[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4-one, Avapro, BMS 186295, Irbesartan

Status : approved

Category

Antihypertensive Agents

Therapeutic Classification

ANGIOTENSIN II ANTAGONISTS, PLAIN

CARDIOVASCULAR SYSTEM
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
ANGIOTENSIN II ANTAGONISTS, PLAIN
Angiotensin II Type 1 Receptor Blockers

Description

Irbesartan is an angiotensin receptor blocker (ARB) used mainly for the treatment of hypertension. It competes with angiotensin II for binding at the AT1 receptor subtype. Unlike ACE inhibitors, ARBs do not have the adverse effect of dry cough. The use of ARBs is pending revision due to findings from several clinical trials suggesting that this class of drugs may be associated with a small increased risk of cancer.

Used

For the treatment of hypertension, as well as diabetic nephropathy with an elevated serum creatinine and proteinuria (>300 mg/day) in patients with type 2 diabetes and hypertension. Irbesartan is also used as a second line agent in the treatment of congestive heart failure.

Mechanism Of Action

Irbesartan is a nonpeptide tetrazole derivative and an angiotensin II antagonist that selectively blocks the binding of angiotensin II to the AT1 receptor. In the renin-angiotensin system, angiotensin I is converted by angiotensin-converting enzyme (ACE) to form angiotensin II. Angiotensin II stimulates the adrenal cortex to synthesize and secrete aldosterone, which decreases the excretion of sodium and increases the excretion of potassium. Angiotensin II also acts as a vasoconstrictor in vascular smooth muscle. Irbesartan, by blocking the binding of angiotensin II to the AT1 receptor, promotes vasodilation and decreases the effects of aldosterone. The negative feedback regulation of angiotensin II on renin secretion is also inhibited, but the resulting rise in plasma renin concentrations and consequent rise in angiotensin II plasma concentrations do not counteract the blood pressure–lowering effect that occurs. The action of ARBs is different from ACE inhibitors, which block the conversion of angiotensin I to angiotensin II, meaning that the production of angiotensin II is not completely inhibited, as the hormone can be formed via other enzymes. Also, unlike ACE inhibitors, irbesartan and other ARBs do not interfere with response to bradykinins and substance P, which allows for the absence of adverse effects that are present in ACE inhibitors (eg. dry cough).

Dosage

Form Route Strength
Tablet oral 25 mg
Tablet, film coated oral 150; 12.5 mg/1; mg
Tablet, film coated oral 300; 12.5 mg/1; mg
Tablet, film coated oral 300; 25 mg/1; mg
Tablet oral 12.5 mg
Tablet oral 150 mg
Tablet oral 300 mg
Tablet oral 75 mg
Tablet, coated oral 150 mg
Tablet, coated oral 300 mg
Tablet, coated oral 75 mg
Tablet, film coated oral 150 mg
Tablet, film coated oral 300 mg
Tablet, film coated oral 75 mg
Tablet oral 150; 12.5 mg/1; mg
Tablet oral 300; 12.5 mg/1; mg
Tablet, film coated oral 12.5; 150 mg/1; mg
Tablet, film coated oral 12.5; 300 mg/1; mg
Tablet oral 25.0 mg

Pharmacodynamics

Angiotensin II, the principal pressor agent of the renin-angiotensin system, is responsible for effects such as vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. 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. Irbesartan’s inhibition of angiotensin II binding to the AT1 receptor leads to multiple effects including vasodilation, a reduction in the secretion of vasopressin, and reduction in the production and secretion of aldosterone. The resulting effect is a decrease in blood pressure.

Toxic Effect

Hypotension and tachycardia; bradycardia might also occur from overdose, LD50=mg/kg(orally in rat)

Metabolism

Hepatic. Irbesartan is metabolized via glucuronide conjugation and oxidation. In vitro studies of irbesartan oxidation by cytochrome P450 isoenzymes indicated irbesartan was oxidized primarily by 2C9; metabolism by 3A4 was negligible.

Absorption

Rapid and complete with an average absolute bioavailability of 60-80%. Food has no affect on bioavailability.

Half Life

11-15 hours

Protein Binding

90% bound to serum proteins (primarily albumin and a1-acid glycoprotein) with negligible binding to cellular components of blood.

Elimination Route

Irbesartan is metabolized via glucuronide conjugation and oxidation. Irbesartan and its metabolites are excreted by both biliary and renal routes. Irbesartan is excreted in the milk of lactating rats.

Clearance

* 157-176 mL/min

Volume of Distribution

* 53 to 93 L

Chemical Classification

This compound belongs to the class of organic compounds known as biphenyltetrazoles and derivatives. These are organic compounds containing a biphenyl attached to a tetrazole. A carbon atom of the biphenyl moiety is boned to a carbon or the nitrogen atom of the tetrazole moiety.

Biphenyltetrazoles and derivatives

Organic compounds

Organoheterocyclic compounds

Azoles

Tetrazoles

Chemical Name

2-Butyl-3-{[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Brands

name Dosage form Country
Act Irbesartan tablet Canada
Act Irbesartan tablet Canada
Act Irbesartan tablet Canada
Act Irbesartan/hct tablet Canada
Act Irbesartan/hct tablet Canada
Act Irbesartan/hct tablet Canada
Apo-irbesartan tablet Canada
Apo-irbesartan tablet Canada
Apo-irbesartan tablet Canada
Apo-irbesartan/hctz tablet Canada
Apo-irbesartan/hctz tablet Canada
Apo-irbesartan/hctz tablet Canada
Auro-irbesartan tablet Canada
Auro-irbesartan tablet Canada
Auro-irbesartan tablet Canada
Ava-irbesartan tablet Canada
Ava-irbesartan tablet Canada
Ava-irbesartan tablet Canada
Ava-irbesartan/hctz tablet Canada
Ava-irbesartan/hctz tablet Canada
Ava-irbesartan/hctz tablet Canada
Avalide tablet, film coated US
Avalide tablet US
Avalide tablet US
Avalide tablet Canada
Avalide tablet, film coated US
Avalide tablet US
Avalide tablet US
Avalide tablet, film coated US
Avalide tablet, film coated US
Avalide tablet, film coated US
Avalide tablet, film coated US
Avalide 150/12.5 mg tablet Canada
Avalide 300/12.5 mg tablet Canada
Avapro tablet US
Avapro tablet US
Avapro tablet US
Avapro tablet Canada
Avapro tablet Canada
Avapro tablet Canada
Avapro tablet US
Avapro tablet US
Avapro tablet US
Avapro tablet US
Avapro tablet US
Avapro tablet US
Avapro tablet US
Avapro tablet US
Avapro tablet US
Avapro tablet US
Dom-irbesartan tablet Canada
Dom-irbesartan tablet Canada
Dom-irbesartan tablet Canada
Dom-irbesartan-hctz tablet Canada
Dom-irbesartan-hctz tablet Canada
Dom-irbesartan-hctz tablet Canada
Ipg-irbesartan tablet Canada
Ipg-irbesartan tablet Canada
Ipg-irbesartan tablet Canada
Irbesartan tablet Canada
Irbesartan tablet Canada
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet Canada
Irbesartan tablet Canada
Irbesartan tablet Canada
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet, coated US
Irbesartan tablet, coated US
Irbesartan tablet, coated US
Irbesartan tablet Canada
Irbesartan tablet Canada
Irbesartan tablet Canada
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet Canada
Irbesartan tablet Canada
Irbesartan tablet Canada
Irbesartan tablet, film coated US
Irbesartan tablet, film coated US
Irbesartan tablet, film coated US
Irbesartan tablet US
Irbesartan tablet Canada
Irbesartan tablet Canada
Irbesartan tablet Canada
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet Canada
Irbesartan tablet Canada
Irbesartan tablet US
Irbesartan tablet Canada
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet US
Irbesartan tablet Canada
Irbesartan and Hydrochlorothiazide tablet US
Irbesartan and Hydrochlorothiazide tablet US
Irbesartan and Hydrochlorothiazide tablet, film coated US
Irbesartan and Hydrochlorothiazide tablet, film coated US
Irbesartan and Hydrochlorothiazide tablet, film coated US
Irbesartan and Hydrochlorothiazide tablet, film coated US
Irbesartan and Hydrochlorothiazide tablet US
Irbesartan and Hydrochlorothiazide tablet US
Irbesartan and Hydrochlorothiazide tablet US
Irbesartan and Hydrochlorothiazide tablet US
Irbesartan and Hydrochlorothiazide tablet, film coated US
Irbesartan and Hydrochlorothiazide tablet, film coated US
Irbesartan and Hydrochlorothiazide tablet, film coated US
Irbesartan and Hydrochlorothiazide tablet, film coated US
Irbesartan and Hydrochlorothiazide tablet, film coated US
Irbesartan and Hydrochlorothiazide tablet US
Irbesartan and Hydrochlorothiazide tablet US
Irbesartan and Hydrochlorothiazide tablet US
Irbesartan and Hydrochlorothiazide tablet US
Irbesartan and Hydrochlorothiazide tablet Canada
Irbesartan and Hydrochlorothiazide tablet Canada
Irbesartan and Hydrochlorothiazide tablet Canada
Irbesartan and Hydrochlorothiazide tablet, film coated US
Irbesartan and Hydrochlorothiazide tablet, film coated US
Irbesartan and Hydrochlorothiazide tablet US
Irbesartan and Hydrochlorothiazide tablet, film coated US
Irbesartan and Hydrochlorothiazide tablet, film coated US
Irbesartan Hct tablet Canada
Irbesartan Hct tablet Canada
Irbesartan Hct tablet Canada
Irbesartan-hctz tablet Canada
Irbesartan-hctz tablet Canada
Irbesartan-hctz tablet Canada
Irbesartan/hct tablet Canada
Irbesartan/hct tablet Canada
Irbesartan/hct tablet Canada
Irbesartan/hctz tablet Canada
Irbesartan/hctz tablet Canada
Irbesartan/hctz tablet Canada
Jamp-irbesartan tablet Canada
Jamp-irbesartan tablet Canada
Jamp-irbesartan tablet Canada
Jamp-irbesartan and Hydrochlorothiazide tablet Canada
Jamp-irbesartan and Hydrochlorothiazide tablet Canada
Jamp-irbesartan and Hydrochlorothiazide tablet Canada
Mint-irbesartan tablet Canada
Mint-irbesartan tablet Canada
Mint-irbesartan tablet Canada
Mint-irbesartan/hctz tablet Canada
Mint-irbesartan/hctz tablet Canada
Mint-irbesartan/hctz tablet Canada
Mylan-irbesartan tablet Canada
Mylan-irbesartan tablet Canada
Mylan-irbesartan tablet Canada
Mylan-irbesartan Hctz tablet Canada
Mylan-irbesartan Hctz tablet Canada
Mylan-irbesartan Hctz tablet Canada
Pendo-irbesartan tablet Canada
Pendo-irbesartan-hctz tablet Canada
PMS-irbesartan tablet Canada
PMS-irbesartan tablet Canada
PMS-irbesartan tablet Canada
PMS-irbesartan-hctz tablet Canada
PMS-irbesartan-hctz tablet Canada
PMS-irbesartan-hctz tablet Canada
Ran-irbesartan tablet Canada
Ran-irbesartan tablet Canada
Ran-irbesartan tablet Canada
Ran-irbesartan Hctz tablet Canada
Ran-irbesartan Hctz tablet Canada
Ran-irbesartan Hctz tablet Canada
Ratio-irbesartan tablet Canada
Ratio-irbesartan tablet Canada
Ratio-irbesartan tablet Canada
Ratio-irbesartan Hctz tablet Canada
Ratio-irbesartan Hctz tablet Canada
Ratio-irbesartan Hctz tablet Canada
Riva-irbesartan tablet Canada
Riva-irbesartan tablet Canada
Riva-irbesartan tablet Canada
Sandoz Irbesartan tablet Canada
Sandoz Irbesartan tablet Canada
Sandoz Irbesartan tablet Canada
Sandoz Irbesartan Hct tablet Canada
Sandoz Irbesartan Hct tablet Canada
Sandoz Irbesartan Hct tablet Canada
Teva-irbesartan tablet Canada
Teva-irbesartan tablet Canada
Teva-irbesartan tablet Canada
Teva-irbesartan/hctz tablet Canada
Teva-irbesartan/hctz tablet Canada
Teva-irbesartan/hctz tablet Canada
Van-irbesartan tablet Canada
Van-irbesartan tablet Canada
Van-irbesartan tablet Canada
Van-irbesartan-hctz tablet Canada
Van-irbesartan-hctz tablet Canada
Van-irbesartan-hctz tablet Canada

Drug Drug Interactions

  •  Alfuzosin  : May enhance the hypotensive effect of Antihypertensives.
  •  Aliskiren  : May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Aliskiren may enhance the hypotensive effect of Angiotensin II Receptor Blockers. Aliskiren may enhance the nephrotoxic effect of Angiotensin II Receptor Blockers.
  •  Amifostine  : Antihypertensives may enhance the hypotensive effect of Amifostine.
  •  Amodiaquine  : CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine.
  •  Aripiprazole  : CYP2D6 Inhibitors (Weak) may increase the serum concentration of Aripiprazole.
  •  Bosentan  : CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Bosentan.
  •  Butabarbital  : May enhance the hypotensive effect of Hypotensive Agents.
  •  Butethal  : May enhance the hypotensive effect of Hypotensive Agents.
  •  Canagliflozin  : May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Canagliflozin may enhance the hypotensive effect of Angiotensin II Receptor Blockers.
  •  Carvedilol  : CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased.
  •  Dapoxetine  : May enhance the orthostatic hypotensive effect of Angiotensin II Receptor Blockers.
  •  Diazoxide  : May enhance the hypotensive effect of Antihypertensives.
  •  Dronabinol  : CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Dronabinol.
  •  Dronabinol  : CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol.
  •  Drospirenone  : Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of Drospirenone.
  •  Duloxetine  : Hypotensive Agents may enhance the orthostatic hypotensive effect of Duloxetine.
  •  Eplerenone  : May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers.
  •  Heparin  : May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers.
  •  Heptabarbital  : May enhance the hypotensive effect of Hypotensive Agents.
  •  Hexobarbital  : May enhance the hypotensive effect of Hypotensive Agents.
  •  Levodopa  : Hypotensive Agents may enhance the orthostatic hypotensive effect of Levodopa.
  •  Lithium  : Angiotensin II Receptor Blockers may increase the serum concentration of Lithium.
  •  Methohexital  : May enhance the hypotensive effect of Hypotensive Agents.
  •  Methylphenidate  : May diminish the antihypertensive effect of Antihypertensives.
  •  Obinutuzumab  : Antihypertensives may enhance the hypotensive effect of Obinutuzumab.
  •  Pentobarbital  : May enhance the hypotensive effect of Hypotensive Agents.
  •  Pentoxifylline  : May enhance the hypotensive effect of Antihypertensives.
  •  Primidone  : May enhance the hypotensive effect of Hypotensive Agents.
  •  Risperidone  : Hypotensive Agents may enhance the hypotensive effect of Risperidone.
  •  Rituximab  : Antihypertensives may enhance the hypotensive effect of Rituximab.
  •  Secobarbital  : May enhance the hypotensive effect of Hypotensive Agents.
  •  Tadalafil  : May enhance the antihypertensive effect of Antihypertensives.
  •  Tolvaptan  : May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers.
  •  Trimethoprim  : May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers.
  •  Vardenafil  : May enhance the antihypertensive effect of Antihypertensives.
  •  Yohimbine  : May diminish the antihypertensive effect of Antihypertensives.

Food Interactions

  • Take without regard to meals.

Calculated Property

kind Value Source
logP 4.51 ALOGPS
logS -4.7 ALOGPS
Water Solubility 8.84e-03 g/l ALOGPS
logP 5.5 ChemAxon
IUPAC Name 2-butyl-3-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1,3-diazaspiro[4.4]non-1-en-4-one ChemAxon
Traditional IUPAC Name irbesartan ChemAxon
Molecular Weight 428.5294 ChemAxon
Monoisotopic Weight 428.232459548 ChemAxon
SMILES CCCCC1=NC2(CCCC2)C(=O)N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NNN=N1 ChemAxon
Molecular Formula C25H28N6O ChemAxon
InChI InChI=1S/C25H28N6O/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) ChemAxon
InChIKey InChIKey=YOSHYTLCDANDAN-UHFFFAOYSA-N ChemAxon
Polar Surface Area (PSA) 87.13 ChemAxon
Refractivity 136.72 ChemAxon
Polarizability 47.59 ChemAxon
Rotatable Bond Count 7 ChemAxon
H Bond Acceptor Count 5 ChemAxon
H Bond Donor Count 1 ChemAxon
pKa (strongest acidic) 7.4 ChemAxon
pKa (strongest basic) 4.12 ChemAxon
Physiological Charge 0 ChemAxon
Number of Rings 5 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 0 ChemAxon
Ghose Filter 0 ChemAxon
MDDR-Like Rule 1 ChemAxon

Affected organism

Humans and other mammals

Target within organism

  • Type-1 angiotensin II receptor : in Human
  • Transcription factor AP-1 : in Human