Despite the introduction of new
antihypertensive agents such as
angiotensin-converting enzyme inhibitors and
calcium channel antagonists, the blood pressure of fewer than 30% of hypertensive patients is controlled with current
therapies; compliance and continuation with medication are poor. The renin-angiotensin system is important in the pathophysiology of
hypertension, end-organ damage and congestive
cardiac failure.
Irbesartan is an
angiotensin II receptor antagonist that provides dose-dependent, specific, insurmountable blockade of the AT1 receptor both in vivo and in vitro. It is rapidly absorbed after
oral administration, has a bioavailability of 60-80% with no food effect, does not require metabolism to a bioactive compound, and is excreted by both biliary and renal routes so that dosage adjustments are unnecessary in patients with renal or hepatic disease.
Irbesartan produces dose-dependent blood pressure reductions, with 24 h activity confirmed by ambulatory blood pressure monitoring.
Irbesartan is effective in the elderly and non-elderly, men and women and in cases of mild and severe
hypertension. The recommended starting dosage is 150 mg once daily (o.d.), which can be increased to 300 mg. Its
antihypertensive effect is accentuated by
diuretic co-administration. In controlled clinical trials,
irbesartan was at least as effective as
atenolol,
hydrochlorothiazide,
amlodipine and
enalapril. In a double-blind study,
irbesartan 300 mg was more effective than
losartan 100 mg, and in a dose-titration study,
irbesartan 150-300 mg produced significantly greater blood pressure reductions than
losartan 50-100 mg. In pooled data from nine placebo-controlled studies, adverse event and discontinuation rates for
irbesartan were similar to those for placebo, and there was no relationship between dose and adverse effects. Preliminary clinical data suggest positive haemodynamic effects in
heart failure and renoprotective effects in
diabetic nephropathy.