Pharmacology: Pharmacodynamics: 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.
Pharmacokinetics: Irbesartan is rapidly absorbed from the gastrointestinal tract with an oral bioavailability of 60 to 80%. It undergoes some metabolism in the liver to inactive metabolites. Peak plasma concentrations of Irbesartan occur 1.5 to 2 hours after an oral dose. Irbesartan is about 90% bound to plasma proteins. It is excreted as unchanged drug and metabolites in the bile and in urine; after oral or intravenous administration approximately 20% of the dose is excreted in the urine, with less than 2% as unchanged drug. The terminal elimination half-life is about 11 to 15 hours.