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: 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 Blood was withdrawn for the measurement of hormones before and 3 h after dosing.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:
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Authors | J M Good, M Peters, M Wilkins, N Jackson, C M Oakley, J G Cleland |
Journal | Journal of the American College of Cardiology
(J Am Coll Cardiol)
Vol. 25
Issue 6
Pg. 1273-81
(May 1995)
ISSN: 0735-1097 [Print] United States |
PMID | 7722120
(Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cyclohexanecarboxylic Acids
- Electrolytes
- Vasoactive Intestinal Peptide
- Aldosterone
- candoxatrilat
- Atrial Natriuretic Factor
- Sodium
- Neprilysin
- Cyclic GMP
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Topics |
- Aged
- Aldosterone
(blood)
- Atrial Natriuretic Factor
(blood)
- Cross-Over Studies
- Cyclic GMP
(urine)
- Cyclohexanecarboxylic Acids
(administration & dosage)
- Diuresis
(drug effects)
- Double-Blind Method
- Drug Administration Schedule
- Electrolytes
(urine)
- Heart Failure
(drug therapy, urine)
- Hemodynamics
(drug effects)
- Humans
- Male
- Middle Aged
- Neprilysin
(antagonists & inhibitors)
- Renal Circulation
(drug effects)
- Sodium
(urine)
- Urine
- Vasoactive Intestinal Peptide
(blood)
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