Substance
ID:905
Names and Identifiers
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
Brand Name
IrbesarranAvaproLrbesartanAvalideIrbesartan [Usan:Inn]
Synonyms
irbesartanIrbesartan
IUPAC Traditional name
irbesartan
Properties
Physical Property
Hydrophobicity(logP)
6
Molecule Details
Drug Groups
approved; investigational
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.
Indication
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.
Pharmacology
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.
Toxicity
Hypotension and tachycardia; bradycardia might also occur from overdose, LD50=mg/kg(orally in rat)
Affected Organisms
Humans and other mammals
Biotransformation
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
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.
Distribution
* 53 to 93 L
Clearance
* 157-176 mL/min
References
•
Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I: Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001 Sep 20;345(12):851-60.
[Pubmed]
•
Adams MA, Trudeau L: Irbesartan: review of pharmacology and comparative properties. Can J Clin Pharmacol. 2000 Spring;7(1):22-31.
[Pubmed]
•
Croom KF, Curran MP, Goa KL, Perry CM: Irbesartan: a review of its use in hypertension and in the management of diabetic nephropathy. Drugs. 2004;64(9):999-1028.
[Pubmed]
External Links
Molecular Spectra
No Data Available
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References
• Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I: Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001 Sep 20;345(12):851-60. Pubmed
• Croom KF, Curran MP, Goa KL, Perry CM: Irbesartan: a review of its use in hypertension and in the management of diabetic nephropathy. Drugs. 2004;64(9):999-1028. Pubmed
• Adams MA, Trudeau L: Irbesartan: review of pharmacology and comparative properties. Can J Clin Pharmacol. 2000 Spring;7(1):22-31. Pubmed