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OtherCARDIOVASCULAR PHARMACOLOGY

Disposition of Vessel Dilator and Long-Acting Natriuretic Peptide in Healthy Humans after a One-Hour Infusion

Bruce H. Ackerman, Rose M. Overton, Michael T. McCormick, Douglas D. Schocken and David L. Vesely
Journal of Pharmacology and Experimental Therapeutics August 1997, 282 (2) 603-608;
Bruce H. Ackerman
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Rose M. Overton
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Michael T. McCormick
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Douglas D. Schocken
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David L. Vesely
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Abstract

The present investigation was designed to determine half-lives, distribution phases and metabolic clearance of two new cardiac peptide hormones in humans. Long-acting natriuretic peptide (LANP) and vessel dilator were infused at 100 ng/kg of b.wt./min concentrations for 60 min with their respective concentrations measured by specific radioimmunoassays in plasma during and for 3 hr after infusion. The half-life of vessel dilator was 107 min, whereas the half-life of LANP was 28 min. The average time that the respective peptides were retained in the body (mean residence time) was 214 ± 34 min for vessel dilator and 178 ± 12 min for LANP, which indicates that they are widely distributed outside the initial space (i.e., circulation). The metabolic clearance normalized to 1.73 m2body surface area was 241 ml/min for vessel dilator and 249 ml/min for LANP. The total body clearance normalized to 1.73 m2 body surface area was 130 ml/min for vessel dilator and 293 ml/min for LANP. The significantly (P < .001) longer half-lives and slower metabolic clearance of LANP and vessel dilator compared with atrial natriuretic factor (half-life, 2.5 min, metabolic clearance, 582–2,581 ml/min/1.7 m2) explain why these peptides circulate at concentrations 15- to 24-fold higher than atrial natriuretic factor in healthy humans.

Footnotes

  • Send reprint requests to: David L. Vesely, M.D. Ph.D., James A. Haley Veterans Hospital-151, 13000 Bruce B. Downs Boulevard, Tampa, FL 33612.

  • ↵1 This work supported in part by a United States Department of Veterans Affairs Merit Review Grant and an American Heart Association Florida Affiliate Grant to Dr. Vesely.

  • ↵2 Present address: SmithKline Beecham Pharmaceuticals, Philadelphia, PA.

  • Abbreviations:
    ANF
    atrial natriuretic factor
    LANP
    long-acting natriuretic peptide
    MRT
    mean residence time
    MC
    metabolic clearance
    BSA
    body surface area
    AUMC
    area under the moment curve
    RIA
    radioimmunoassay
    AUC
    area under concentration curves
    TBC
    total body clearance
    VdB
    β-distribution volume
    a.a.
    amino acid(s)
    HPLC
    high-pressure liquid chromatography
    VC
    volume of distribution of central compartment
    • Received June 25, 1996.
    • Accepted April 7, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 282, Issue 2
1 Aug 1997
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OtherCARDIOVASCULAR PHARMACOLOGY

Disposition of Vessel Dilator and Long-Acting Natriuretic Peptide in Healthy Humans after a One-Hour Infusion

Bruce H. Ackerman, Rose M. Overton, Michael T. McCormick, Douglas D. Schocken and David L. Vesely
Journal of Pharmacology and Experimental Therapeutics August 1, 1997, 282 (2) 603-608;

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Disposition of Vessel Dilator and Long-Acting Natriuretic Peptide in Healthy Humans after a One-Hour Infusion

Bruce H. Ackerman, Rose M. Overton, Michael T. McCormick, Douglas D. Schocken and David L. Vesely
Journal of Pharmacology and Experimental Therapeutics August 1, 1997, 282 (2) 603-608;
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