A DOSE-RESPONSE STUDY TO ASSESS THE RENAL HEMODYNAMIC, VASCULAR, AND HORMONAL EFFECTS OF EPROSARTAN, AN ANGIOTENSIN-II AT(1)-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-bli nd, 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 201) mg eprosartan; and part 3 (n = 5) assessed the duration of th e effect of 50, 100, or 350 mg eprosartan. Results: In part 1 of the s tudy, 350 mg eprosartan caused complete inhibition of angiotensin II-i nduced presser and renal blood flow hemodynamic effects (effects on ef fective renal plasma flow [ERPF]) and inhibited angiotensin IT-induced stimulation of aldosterone secretion from 1 to 3 hours after administ ration. Eprosartan, 350 mg, inhibited the effects of exogenous angiote nsin II by approximately 50% to 70% from 12 to 15 hours after dosing. Eprosartan had no angiotensin II agonistic activity and produced an in crease 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, epr osartan inhibited angiotensin II-induced decreases in ERPF by 39.1%, 4 9.9%, 33.0%, 56.0%, 71.0%, and 85.7%, respectively, compared with plac ebo. In study part 3, 50, 100, and 350 mg eprosartan produced measurab le inhibition of angiotensin II-induced decreases in ERPF from 12 to 1 5 hours after administration. In parts 2 and 3, the eprosartan angiote nsin IT antagonism on blood pressure response and aldosterone secretio n mirrored the angiotensin II antagonism on ERPF.