Vol. 282, Issue 2, 603-608, 1997

Disposition of Vessel Dilator and Long-Acting Natriuretic Peptide in Healthy Humans after a One-Hour Infusion¹

Bruce H. Ackerman² , Rose M. Overton, Michael T. McCormick, Douglas D. Schocken and David L. Vesely

Department of Pharmacy Practice and Pharmacy Administration, Philadelphia College of Pharmacy and Science, Philadelphia, Pennsylvania (B.H.A.), and Departments of Internal Medicine (R.M.O., D.D.S., D.L.V.) and Pharmacy (M.T.M.), James A. Haley Veterans Hospital and University of South Florida Health Sciences Center, Tampa, Florida

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 m² body 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.