title: 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.
abstract: METHODS
  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.
authors.affiliation: SmithKline Beecham Clinical Pharmacology Unit, Presbyterian Medical Center of Philadelphia 19104, USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Ilson
authors.forename: S C
authors.initials: SC
authors.lastname: Boike
authors.forename: D E
authors.initials: DE
authors.lastname: Martin
authors.forename: M I
authors.initials: MI
authors.lastname: Freed
authors.forename: N
authors.initials: N
authors.lastname: Zariffa
authors.forename: D K
authors.initials: DK
authors.lastname: Jorkasky
mesh_terms: D000179:Acrylates / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D017419:Potassium, Dietary / Q000008:administration & dosage; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects*; D012982:Sodium, Dietary / Q000008:administration & dosage; D013876:Thiophenes; D013997:Time Factors
chemical_list: D000179:Acrylates; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D017419:Potassium, Dietary; D012982:Sodium, Dietary; D013876:Thiophenes; C068373:eprosartan; D000450:Aldosterone