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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
Author(s) -
Ilson Bernard E.,
Boike Steven C.,
Martin David E.,
Freed Martin I.,
Zariffa Névine,
Jorkasky Diane K.
Publication year - 1998
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(98)90043-1
Subject(s) - effective renal plasma flow , angiotensin ii , aldosterone , medicine , endocrinology , angiotensin ii receptor type 1 , renal blood flow , renin–angiotensin system , pharmacology , chemistry , hemodynamics , blood pressure
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 II‐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. Clinical Pharmacology & Therapeutics (1998) 63 , 471–481; doi: