TY - JOUR T1 - Disposition of Vessel Dilator and Long-Acting Natriuretic Peptide in Healthy Humans after a One-Hour Infusion JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 603 LP - 608 VL - 282 IS - 2 AU - Bruce H. Ackerman AU - Rose M. Overton AU - Michael T. McCormick AU - Douglas D. Schocken AU - David L. Vesely Y1 - 1997/08/01 UR - http://jpet.aspetjournals.org/content/282/2/603.abstract N2 - 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. The American Society for Pharmacology and Experimental Therapeutics ER -