Brands, Medical Use, Clinical Data
- Antihypertensive Agents
- Angiotensin II Receptor Antagonists
Brands / Synonyms
Avalide; Avapro; Irbesarran; Irbesartan [Usan:Inn]; Lrbesartan
For the treatment of hypertension, and for the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria (>300 mg/day) in patients with type 2 diabetes and hypertension.
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.
Mechanism of Action
Irbesartan is a nonpeptide 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 also is 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.
Rapid and complete with an average absolute bioavailability of 60-80%. Food has no affect on bioavailability.
Hypotension and tachycardia; bradycardia might also occur from overdose, LD50=mg/kg(orally in rat)
Biotrnasformation / Drug 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.
AVAPRO is contraindicated in patients who are hypersensitive to any component of this product.
No significant drug-drug pharmacokinetic (or pharmacodynamic) interactions have been found in
interaction studies with hydrochlorothiazide, digoxin, warfarin, and nifedipine.
In vitro studies show significant inhibition of the formation of oxidized irbesartan
metabolites with the known cytochrome CYP 2C9 substrates/inhibitors sulphenazole, tolbutamide and nifedipine.
However, in clinical studies the consequences of concomitant irbesartan on the pharmacodynamics of warfarin were
negligible. Based on in vitro data, no interaction would be expected with drugs whose metabolism is dependent
upon cytochrome P450 isozymes 1A1, 1A2,2A6,2B6,2D6,2E1,or 3A4.
In separate studies of patients receiving maintenance doses of warfarin, hydrochlorothiazide, or
digoxin, irbesartan administration for 7 days had no effect on the pharmacodynamics of warfarin (prothrombin time) or
pharmacokinetics of digoxin. The pharmacokinetics of irbesartan were not affected by coadministration of nifedipine