TY - JOUR
T1 - Dose-ranging effects of candoxatril on elimination of exogenous atrial natriuretic peptide in chronic heart failure
AU - Motwani, Joseph G.
AU - Lang, Chim C.
AU - Allen, Michael J.
AU - Johnson, Helen F.
AU - Struthers, Allan D.
N1 - Supported in part by a grant from Pfizer Central Research (Sandwich, Kent, England). Dr. Motwani was supported by the Scottish Hospital Endowments Research Trust (Edinburgh, Scotland). Dr. Struthers was supported by the Wellcome Trust (Crewe, Cheshire, England).
PY - 1993
Y1 - 1993
N2 - Seven patients with chronic heart failure were treated in single-blind crossover fashion with placebo and 10 mg, 50 mg, and 200 mg doses of the neutral endopeptidase inhibitor candoxatril to determine the effects of candoxatril on the elimination kinetics of exogenously infused atrial natriuretic peptide (ANP). An incremental dose-response effect was observed on the mean maximum observed plasma concentration (Cmax) of the active metabolite candoxatrilat (107.4, 453.5, and 1584 ng/ml in response to 10, 50, and 200 mg candoxatril, respectively). Pooled active versus placebo comparisons showed that candoxatril reduced the clearance (p = 0.021) and elimination rate constant (p = 0.006) and increased Cmax (p = 0.002) and time to reach Cmax (p = 0.01) of exogenous ANP. Individually, both 50 mg and 200 mg but not 10 mg candoxatril significantly altered the elimination kinetics of ANP. The most favorable effects were observed in response to 200 mg candoxatril, although even this dose may not have achieved the maximal modulating effect on elimination of circulating ANP.
AB - Seven patients with chronic heart failure were treated in single-blind crossover fashion with placebo and 10 mg, 50 mg, and 200 mg doses of the neutral endopeptidase inhibitor candoxatril to determine the effects of candoxatril on the elimination kinetics of exogenously infused atrial natriuretic peptide (ANP). An incremental dose-response effect was observed on the mean maximum observed plasma concentration (Cmax) of the active metabolite candoxatrilat (107.4, 453.5, and 1584 ng/ml in response to 10, 50, and 200 mg candoxatril, respectively). Pooled active versus placebo comparisons showed that candoxatril reduced the clearance (p = 0.021) and elimination rate constant (p = 0.006) and increased Cmax (p = 0.002) and time to reach Cmax (p = 0.01) of exogenous ANP. Individually, both 50 mg and 200 mg but not 10 mg candoxatril significantly altered the elimination kinetics of ANP. The most favorable effects were observed in response to 200 mg candoxatril, although even this dose may not have achieved the maximal modulating effect on elimination of circulating ANP.
U2 - 10.1038/clpt.1993.204
DO - 10.1038/clpt.1993.204
M3 - Article
C2 - 8275621
SN - 0009-9236
VL - 54
SP - 661
EP - 669
JO - Clinical Pharmacology & Therapeutics
JF - Clinical Pharmacology & Therapeutics
IS - 6
ER -