Candesartan cilexetil: a new, long-acting, effective angiotensin II type 1 receptor blocker

Abstract

Candesartan is a potent and selective angiotensin II type 1 receptor blocker which binds tightly to and dissociates slowly from the AT1 receptor. It is administered orally as the prodrug candesartan cilexetil, which is rapidly and completely converted to the active compound, candesartan, during gastrointestinal absorption. In hypertensive patients, candesartan cilexetil dose-dependently lowers diastolic and systolic blood pressure (BP) over the 24-h dose interval and it maintains its antihypertensive effects in the long term. Clinical trials indicate that a once-daily dose of 4-16 mg provides a clinically relevant reduction in BP. The usual maintenance doses of candesartan cilexetil are expected to be 8 mg and 16 mg once-daily and dosage adjustment does not appear to be necessary in elderly patients or those with mild to moderate renal or hepatic impairment. Adverse events during treatment with candesartan cilexetil occur at a similar low incidence as with placebo and no dose-dependent events or adverse metabolic effects have been noted. As once-daily monotherapy, candesartan cilexetil 8 mg is as effective as enalapril 10-20 mg, amlodipine 5 mg or hydrochlorothiazide 25 mg, and candesartan cilexetil 16 mg is more effective than losartan 50 mg. The trough to peak ratio for the reduction in BP with candesartan cilexetil has been shown to be in the order of 80-100%, confirming the smooth 24-h BP-lowering profile of the drug. Combined treatment with candesartan cilexetil and hydrochlorothiazide or amlodipine provides an enhanced BP-lowering effect that is useful in patients with inadequate response to initial treatment after step-up titration. Candesartan cilexetil is similarly well tolerated as placebo, both when given as monotherapy, and in combination for example with hydrochlorothiazide. Candesartan cilexetil with its flexible dosage regimen therefore appears to offer an effective and well-tolerated alternative to other established agents in the treatment of a wide range of hypertensive patients.