Pharmacotherapeutic Group: Angiotensin-II antagonists, plain. 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 of 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 litres. Irbesartan is metabolised by the liver via glucuronide conjugation and oxidation. The major circulating metabolite is irbesartan glucuronide (approximately 6%).
Peak plasma concentrations are attained at 1.5 - 2 hours after oral administration. The total body and renal clearance are 157 - 176 and 3 - 3.5 ml/min, respectively. The terminal elimination half-life of irbesartan is 11 - 15 hours. Steady-state plasma concentrations are attained within 3 days after initiation of a once-daily dosing regimen. Limited accumulation of irbesartan (< 20%) is observed in plasma upon repeated once-daily dosing. No dosage adjustment is necessary in female patients. Irbesartan AUC and Cmax values were also somewhat greater in older subjects (≥ 65 years) than those of young subjects (18 - 40 years).
However the terminal half-life was not significantly altered. No dosage adjustment is necessary in older people.
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.