CANDESARTAN CILEXETIL, A NEW-GENERATION ANGIOTENSIN-II ANTAGONIST, PROVIDES DOSE-DEPENDENT ANTIHYPERTENSIVE EFFECT

Candesartan is a new generation angiotensin II type 1 receptor blocker , characterised by tight binding to and slow dissociation from the rec eptor. In order to delineate the dose-response curve for candesartan c ilexetil (the orally administered prodrug), results from six European placebo-controlled, dose-response studies were pooled. These were of a double-blind, randomised, parallel group design, with a treatment dur ation of 4-12 weeks. A total of 1482 patients with mild to moderate pr imary hypertension were treated with candesartan cilexetil 2 mg (n = 8 0), 4 mg (n = 216), 8 mg (n = 455) or 16 mg (n = 294), or with placebo (n = 437). Blood pressure (BP) measurements were performed 24 h after dose. The differences in BP change (baseline vs end of the studies) b etween the placebo group and the groups treated with candesartan cilex etil were assessed using analysis of covariance and dose response curv es were estimated by fitting the data to an E-max model. The placebo-c orrected mean reductions in sitting diastolic BP were approximately 2. 5 mm Hg with 2 mg, 4.5 mm Hg with 4 mg, 6 mm Hg with 8 mg, and 8 mm Hg with 16 mg of candesartan cilexetil. For sitting systolic BP, the pla cebo-corrected mean reductions were in the order of 5, 7, 10 and 12 mm Hg, respectively, with 2, 4, 8 and 16 mg of candesartan cilexetil. The BP reductions were similar in the standing position with no indicatio n of postural hypotension. Age or gender did not influence the BP resp onse to candesartan cilexetil. In conclusion, candesartan cilexetil pr ovides a clinically significant, dose-dependent antihypertensive effec t in doses ranging from 4-16 mg once daily.