Irbevex 150/Irbevex 300 Mechanism of Action

Pharmacological Classification: Angiotensin II receptor Blocker.
Pharmacology: Pharmacodynamics: Mechanism of action: Angiotensin II is the primary vasoactive hormone in the renin-angiotensin system. Its effects include vasoconstriction and the stimulation of aldosterone secretion by the adrenal cortex.
Irbesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking in a non competitive manner the binding of angiotensin II to the AT₁ receptor found in many tissues. Irbesartan has no agonist activity at the AT1 receptor. AT₂ receptors have been found in many tissues, but to date they have not been associated with cardiovascular homeostasis. Irbesartan has essentially no affinity for the AT2 receptors.
Irbesartan does not inhibit angiotensin converting enzyme, also known as kininase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin, nor does it affect renin or other hormone receptors or ion channels involved in cardiovascular regulation of blood pressure and sodium homeostasis.
Pharmacokinetics: Irbesartan is an orally active agent. The oral absorption of Irbesartan is rapid and complete with an average absolute bioavailability of 60% - 80%. Irbesartan exhibits linear pharmacokinetics over the therapeutic dose range with an average terminal elimination half-life of 11-15 hours.
Following oral administration, peak plasma concentrations are attained at 1.5-2 hours after Dosing. Steady-state concentrations are achieved within 3 days.
Irbesartan is approximately 96% protein-bound in the plasma, primarily to albumin and α1-acid glycoprotein.
The average volume of distribution of Irbesartan is 53-93 liters. Total plasma and renal clearances are in the range of 157 - 176 and 3.0 - 3.5 mL/minute, respectively.
Irbesartan is metabolized via glucuronide conjugation and oxidation by the cytochrome P-450 system. Following either oral or intravenous administration of ¹⁴C-labeled Irbesartan, more than 80% of the circulating plasma radioactivity is attributable to unchanged Irbesartan. The primary circulating metabolite is the inactive Irbesartan glucuronide (approximately 6%). The remaining oxidative metabolites do not add appreciably to the pharmacologic activity. Irbesartan and its metabolites are excreted by both biliary and renal routes. Following either oral or intravenous administration of ¹⁴C-labeled Irbesartan, about 20% of radioactivity is recovered in the urine and the remainder in the feces. Less than 2% of the dose is excreted in urine as unchanged Irbesartan.