Dose-ranging effects of candoxatril on elimination of exogenous atrial natriuretic peptide in chronic heart failure

Joseph G. Motwani, Chim C. Lang, Michael J. Allen, Helen F. Johnson, Allan D. Struthers

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)661-669
Number of pages9
JournalClinical Pharmacology & Therapeutics
Volume54
Issue number6
DOIs
Publication statusPublished - 1993

Fingerprint Dive into the research topics of 'Dose-ranging effects of candoxatril on elimination of exogenous atrial natriuretic peptide in chronic heart failure'. Together they form a unique fingerprint.

  • Cite this