Metabolism and action of urodilatin infusion in healthy volunteers.
OBJECTIVE
The objective of this investigation was to study both the pharmacokinetics and renal pharmacodynamic properties of intravenously infused urodilatin in human beings.


METHODS
Twelve healthy subjects received a short-term infusion (90 minutes) of urodilatin and placebo with a graded infusion rate (from 7.5 to 15 to 30 ng.kg body weight-1.min-1) in a randomized, double-blind, crossover study design. The renal parameters were evaluated by clearance technique with the use of 51Cr-ethylenediaminetetraacetic acid, 125I-hippuran, and lithium. Urodilatin concentrations were determined by a radioimmunoassay with a urodilatin-specific antibody.


RESULTS
Kinetics were characterized by a high apparent volume of distribution (43.7 +/- 11.2 L), a high total body clearance (5383 +/- 581 ml/min), and a short plasma half-life (5.57 +/- 0.8 minutes). The maximal plasma urodilatin level was 177.2 +/- 25.8 pmol/L. Less than 1% of total infused urodilatin was recovered in urine. Urodilatin significantly increased glomerular filtration rate (urodilatin, 7.0%, versus placebo, -1.9%; p < 0.05), reduced effective renal plasma flow (urodilatin, -17%, versus placebo, -3%; p < 0.01), increased fractional excretion of sodium (urodilatin, 137%, versus placebo, 27%; p < 0.05), and increased urine flow rate (urodilatin, 46%, versus placebo, -15%; p < 0.01). Fractional excretion of lithium did not change. Mean blood pressure decreased and vasoactive hormone levels remained unchanged or increased.


CONCLUSIONS
The natriuretic and diuretic effects of urodilatin closely followed the profile of urodilatin concentration in plasma. A major part of the synthetic urodilatin was removed from circulation by a route other than filtration through the glomeruli.
Research Laboratory of Nephrology and Hypertension, Aarhus University Hospital, Denmark.
J
J
Carstens
K T
KT
Jensen
E B
EB
Pedersen
D000328:Adult; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000187:drug effects / Q000378:metabolism; D001127:Arginine Vasopressin / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D018592:Cross-Over Studies; D006152:Cyclic GMP / Q000378:metabolism; D004232:Diuretics / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008094:Lithium / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D012083:Renin / Q000097:blood / Q000187:drug effects; D012964:Sodium / Q000652:urine
D004232:Diuretics; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D000804:Angiotensin II; D001127:Arginine Vasopressin; D020097:Natriuretic Peptide, Brain; D000450:Aldosterone; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D008094:Lithium; D012964:Sodium; D012083:Renin; D006152:Cyclic GMP