EC 24.11 Inhibition in Man Alters Clearance of Atrial Natriuretic Peptide*
Why the study?
Does candoxatril alter the metabolic clearance and biological effects of exogenous atrial natriuretic peptide in normal volunteers?
Population
16 normal volunteers (two groups of 8)
Comparison
Candoxatril for 5 days, with a 2-hour… vs Placebo for 5 days, with a 2-hour intravenous…
Design
RCT, balanced randomized, cross-over, double blind, placebo-controlled
Follow-up
5 days
Authors
Discussion
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Implication
Candoxatril reduces exogenous ANF clearance and amplifies its effects; confirms endopeptidase 24.11 inhibition as a viable strategy to potentiate natriuretic peptides.
Key Points
- To determine whether oral inhibition of endopeptidase 24.11 by candoxatril alters the metabolic clearance and physiological actions of infused atrial natriuretic factor in humans.
- Balanced randomized, double-blind, placebo-controlled, cross-over trial in 16 healthy volunteers split into two groups of eight.
- Participants received oral candoxatril (group 1: 25 mg every 12 h; group 2: 100 mg every 12 h) or placebo for five days, alongside a 2-h intravenous infusion of atrial natriuretic factor (2.5 pmol/kg·min) on day five.
- Candoxatril significantly decreased atrial natriuretic factor metabolic clearance rates in group 1 (2.5 ± 0.4 vs. 4.3 ± 0.6 L/min; P < 0.01) and group 2 (2.3 ± 0.4 vs. 5.6 ± 0.8 L/min; P < 0.001).
- Pretreatment with 100 mg candoxatril enhanced infusion-induced rises in plasma atrial natriuretic factor by 42 pmol/L (P < 0.002) and significantly amplified urinary sodium excretion (P < 0.01).
- Renal filtration fractions increased with candoxatril in group 1 (15.5 ± 0.5% vs. 13.9 ± 0.6%; P < 0.01) and group 2 (19.3 ± 1.9% vs. 18.0 ± 2.7%; P < 0.01), along with significant increases in plasma and urinary cGMP.
Structured PICO
Does candoxatril alter the metabolic clearance and biological effects of exogenous atrial natriuretic peptide in normal volunteers?
P
Population
16 normal volunteers (two groups of 8)
I
Intervention
Candoxatril (25 mg every 12 h in group 1, 100 mg every 12 h in group 2) for 5 days, with a 2-hour intravenous infusion of human atrial natriuretic factor (ANF) (2.5 pmol/kg.min) on the fifth day
C
Comparator
Placebo for 5 days, with a 2-hour intravenous infusion of human ANF on the fifth day (cross-over design)
O
Outcome
Metabolic clearance and biological effects of exogenous human atrial natriuretic factor (ANF)surrogate
Inhibition of endopeptidase 24.11 with candoxatril reduces the metabolic clearance of exogenous ANF, amplifying its physiological effects including natriuresis and cGMP generation.
Cite This Study
Richards et al. (1991) studied this question.