A dose-response study to assess the renal hemodynamic, vascular, and hormonal effects of eprosartan, an angiotensin II AT1-receptor antagonist, in sodium-replete healthy men.

STUDY DESIGN

The effects of orally administered eprosartan on changes induced by angiotensin II in blood pressure, renal hemodynamics, and aldosterone secretion were evaluated in healthy men in this double-blind, randomized, single-dose, placebo-controlled crossover study, which was conducted in three parts. Part 1 (n = 12) assessed the onset and duration of the effect of eprosartan 350 mg or placebo; part 2 (n = 14) assessed the dose-response profile of placebo or 10, 30, 50, 70, 100 or 200 mg eprosartan; and part 3 (n = 5) assessed the duration of the effect of 50, 100, or 350 mg eprosartan.

RESULTS

In part 1 of the study; 350 mg eprosartan caused complete inhibition of angiotensin II-induced pressor and renal blood flow hemodynamic effects (effects on effective renal plasma flow [ERPF]) and inhibited angiotensin II-induced stimulation of aldosterone secretion from 1 to 3 hours after administration. Eprosartan, 350 mg, inhibited the effects of exogenous angiotensin II by approximately 50% to 70% from 12 to 15 hours after dosing. Eprosartan had no angiotensin II agonistic activity and produced an increase in ERPF starting at 1 to 4 hours after dosing. In study part 2, at 3 hours after single doses of 10, 30, 50, 70, 100, and 200 mg, eprosartan inhibited angiotensin 11-induced decreases in ERPF by 39.1%, 49.9%, 33.0%, 56.0%, 71.0%, and 85.7%, respectively, compared with placebo. In study part 3, 50, 100, and 350 mg eprosartan produced measurable Inhibition of angiotensin II-induced decreases in ERPF from 12 to 15 hours after administration. In parts 2 and 3, the eprosartan angiotensin II antagonism on blood pressure response and aldosterone secretion mirrored the angiotensin II antagonism on ERPF.