Hemodynamic and Biochemical Effects of the AT ₁ Receptor Antagonist Irbesartan in Hypertension

Abstract

We studied the hemodynamic, neurohumoral, and biochemical effects of the novel angiotensin type 1 (AT1) receptor antagonist irbesartan in 86 untreated patients with essential hypertension on a normal sodium diet. According to a double-blind parallel group trial, patients were randomized to a once-daily oral dose of the AT1 receptor antagonist (1, 25, or 100 mg) or placebo after a placebo run-in period of 3 weeks. Randomization medication was given for 1 week. Compared with placebo, 24-hour ambulatory blood pressure did not change with the 1-mg dose, and it fell (mean and 95% confidence interval) by 7.0 (4.2-9.8)/6.1 (3.9-8.1) mm Hg with the 25-mg dose and by 12.1 (8.1-16.2)/7.2 (4.9-9.4) mm Hg with the 100-mg dose. Heart rate did not change during either dose. With the 25-mg dose, the antihypertensive effect was attenuated during the second half of the recording, and with the 100-mg dose, it was maintained for 24 hours. Baseline values of renin and the antihypertensive response to the 25- and 100-mg doses were well correlated (r = .68, P < .01). Renin did not change with the 1-mg dose, but it rose threefold to fourfold with the 25-mg dose and fourfold to fivefold with the 100-mg dose 4 to 6 hours after administration. With the 100-mg dose, renin was still elevated twofold 24 hours after dosing. The changes in renin induced by the AT1 receptor antagonist were associated with parallel increments in angiotensin I and angiotensin II. Aldosterone, despite AT1 receptor blockade, did not fall.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension

“…Treatment with the ARBs does not result in clinically significant alterations in laboratory measurements of serum chemistry, haematology and urinalysis. [2][3][4][5][6][7][8][9][10][11][12][13][14][15]19,23,39,44,50,59,62,81 The ARBs do not impair glucose or lipid metabolism. [2][3][4][5][6][7][8][9][10][11][12][13][14][15]19,[81][82][83] These drugs have no adverse effect on renal function.…”

“…6,10,14,15,27 The drug exhibits nearly linear dose-response (blood pressure lowering) relationship for 50-300 mg dose. 6,10,23,27,32,46 After oral dosing, maximum blood pressure lowering effect occurs at 3-6 h. 6,14,15 Peak efficacy of blood pressure lowering effect is reached in 4 -8 weeks. 6,10,14,15 Irbesartan is effective in hypertensive patients, irrespective of S77 age or gender.…”

“…The ARBs have a low incidence of adverse effects, [2][3][4][5][6][7][8][9][10][11][12][13][14][15][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]42,44,[46][47][48][49][50][51][52][53][54][55][56][57][58][59]62,63,[76][77]<...>…”

A randomised, double-blind comparison of the angiotensin II receptor antagonist, irbesartan, with the full dose range of enalapril for the treatment of mild-to-moderate hypertension

“…14,15 Results of recent clinical studies show that irbesartan safely and effectively lowers blood pressure within 1 week in patients with mild-tomoderate hypertension. 15,16 The objective of this study was to compare the anti-hypertensive efficacy, safety, and tolerability of irbesartan with those of the full dose range of the ACE inhibitor enalapril, in patients with mild-tomoderate hypertension.…”

Comparison of irbesartan vs felodipine in the regression after 1 year of left ventricular hypertrophy in hypertensive patients (The SILVER trial)

“…26 However, recent evidence indicates that in spontaneously hypertensive rats, although an angiotensin-II receptor antagonist lowered BP to a comparable degree compared to an ACE inhibitor or calcium-channel blocker, it caused regression of LVH to a greater extent than the latter. 27 Irbesartan (SR 47436;BMS 186295) is a new anti-hypertensive agent [28][29][30] belonging to this class. [31][32][33] The aim of the present study is to ascertain the effect of irbesartan on LVH, versus a calcium channel blocker, felodipine.…”