Irbevell Mechanism of Action

Pharmacology: Pharmacodynamics: Irbesartan is a nonpeptide competitive angiotensin II antagonist that selectively blocks the binding of angiotensin II to the AT 1 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 AT 1 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: Absorption: Irbesartan is rapidly absorbed from the gastrointestinal tract with an oral bioavailability of 60 to 80%. Peak plasma concentrations of irbesartan occur 1.5 to 2 hours after an oral dose. Irbesartan may be dosed without regards to meals.
Distribution: Irbesartan is about 96% bound to plasma proteins. The volume of distribution is 53 - 93 litres.
Metabolism: Irbesartan is metabolised in the liver via glucuronide conjugation and oxidation, primarily by the cytochrome P450 isoenzyme CYP2C9, to inactive metabolites. The major circulating metabolite is irbesartan glucuronide (approximately 6%).
Elimination: It is excreted as unchanged drug and metabolites in the bile and in urine. The terminal elimination half-life is about 11 to 15 hours. The total body clearance is 157 - 176 ml/min.