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Title: Pharmacology of irbesartan.
Austin Authors: Johnston, Colin I
Affiliation: Department of Medicine, University of Melbourne, Austin Campus, Heidelberg 3084, Victoria, Australia
Issue Date: 1-May-1999
Publication information: Expert Opinion On Investigational Drugs; 8(5): 655-70
Abstract: 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.
Gov't Doc #: 15992121
DOI: 10.1517/13543784.8.5.655
Journal: Expert opinion on investigational drugs
Type: Journal Article
Appears in Collections:Journal articles

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