Disposition of vessel dilator and long-acting natriuretic peptide in healthy humans after a one-hour infusion.
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.
Ackerman
B H
BH
Department of Pharmacy Practice and Pharmacy Administration, Philadelphia College of Pharmacy and Science, Pennsylvania, USA.
Overton
R M
RM
McCormick
M T
MT
Schocken
D D
DD
Vesely
D L
DL
D000328:Adult; D019540:Area Under Curve; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D005260:Female; D006207:Half-Life; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D014665:Vasodilator Agents; D009320:Atrial Natriuretic Factor