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Renal response to candoxatrilat in patients with heart failure.

Abstract：

OBJECTIVES:Our primary objective was to compare the effects of three different doses of candoxatrilat with the effects of placebo on urinary volume in patients with moderately severe heart failure. The effects of candoxatrilat on urinary composition, neuroendocrine indexes and renal hemodynamic function were also studied. BACKGROUND:Candoxatrilat, a neutral endopeptidase inhibitor, reduces degradation of atrial natriuretic peptide and provokes diuresis in patients with mild heart failure, but the renal effects have not been studied in patients with moderately severe heart failure in a placebo-controlled study. METHODS:In a double-blind crossover trial, the effects of intravenous boluses of saline vehicle (placebo) and 50, 100 and 200 mg of candoxatrilat were compared on separate days in 12 patients with heart failure. Urinary output and composition were measured for 8 h. Renal blood flow and glomerular filtration rate were determined by radionuclide techniques. Blood was withdrawn for the measurement of hormones before and 3 h after dosing. RESULTS:All doses of candoxatrilat increased urinary volume (e.g., [mean +/- SEM] 263 +/- 53 to 490 +/- 82 ml for saline solution and the 200-mg dose, respectively, p < 0.01) and sodium content (14 +/- 4 to 37 +/- 11 mmol, p < 0.001) in the 1st 4 h after dosing. Plasma atrial natriuretic peptide increased (140 +/- 26 to 279 +/- 37 pg/ml, p < 0.01), whereas aldosterone decreased (178 +/- 41 to 125 +/- 35 pg/ml, p < 0.01), and renin activity was unchanged (10 +/- 2 to 12 +/- 3 ng/ml per h). CONCLUSIONS:Candoxatrilat given acutely causes diuresis, even in patients with moderately severe heart failure.

journal_name

J Am Coll Cardiol

journal_title

Journal of the American College of Cardiology

authors

Good JM,Peters M,Wilkins M,Jackson N,Oakley CM,Cleland JG

doi

10.1016/0735-1097(94)00561-4

subject

Has Abstract

pub_date

1995-05-01 00:00:00

pages

1273-81

issue

6

eissn

0735-1097

issn

1558-3597

pii

0735-1097(94)00561-4

journal_volume

25

pub_type

临床试验,杂志文章,随机对照试验

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