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

Clin Pharmacol Ther. 1998 Apr;63(4):471-81. doi: 10.1016/S0009-9236(98)90043-1.

Abstract

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylates / administration & dosage
  • Acrylates / pharmacology*
  • Adult
  • Aldosterone / blood
  • Aldosterone / metabolism*
  • Angiotensin Receptor Antagonists*
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / pharmacology*
  • Blood Pressure / drug effects*
  • Dose-Response Relationship, Drug
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / pharmacology*
  • Male
  • Potassium, Dietary / administration & dosage
  • Reference Values
  • Renal Circulation / drug effects*
  • Sodium, Dietary / administration & dosage
  • Thiophenes*
  • Time Factors

Substances

  • Acrylates
  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Imidazoles
  • Potassium, Dietary
  • Sodium, Dietary
  • Thiophenes
  • eprosartan
  • Aldosterone