Irbis Mechanism of Action

Pharmacotherapeutic Group: Angiotensin-II antagonists. ATC Code: C09C A04.
Pharmacology: Pharmacodynamics: Mechanism of action: Irbesartan is a potent, orally active, selective angiotensin-II receptor (type AT1) antagonist.
It is expected to block all actions angiotensin-II mediated by the AT1 receptor, regardless of the source or route of synthesis of angiotensin-II. The selective antagonism of the angiotensin-II (AT1) receptors results in increases in plasma renin levels and angiotensin-II levels, and a decrease in plasma aldosterone concentration. Serum potassium levels are not significantly affected by irbesartan alone at the recommended doses. Irbesartan does not inhibit ACE (kininase-II), an enzyme which generates angiotensin-II and also degrades bradykinin into inactive metabolites. Irbesartan does not require metabolic activation for its activity.
Pharmacokinetics: After oral administration, irbesartan is well absorbed studies of absolute bioavailability gave values of approximately 60 - 80%. Concomitant food intake does not significantly influence the bioavailability of irbesartan. Plasma protein binding is approximately 96%, with negligible binding to cellular blood components. The volume of distribution is 53 - 93 liters. Following oral or intravenous administration of 14C irbesartan, 80-85% of the circulating plasma radioactivity is attributable to unchanged irbesartan. Irbesartan is metabolized by the liver via glucuronide conjugation and oxidation.
The major circulating metabolite is irbesartan glucuronide (approximately 6%). In vitro studies indicate that irbesartan is primarily oxidized by the cytochrome P450 enzyme CYP2C9; isoenzyme CYP3A4 has negligible effect.
Renal impairment: In patients with renal impairment or those undergoing haemodialysis, the pharmacokinetic parameters of irbesartan are not significantly altered. Irbesartan is not removed by haemodialysis.
Hepatic impairment: In patients with mild to moderate cirrhosis, the pharmacokinetic parameters of irbesartan are not significantly altered. Studies have not been performed in patients with severe hepatic impairment.