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
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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.
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↵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.
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↵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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