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Metabolism and action of urodilatin infusion in healthy volunteers
Author(s) -
Carstens Jan,
Jensen Kaare T.,
Pedersen Erling B.
Publication year - 1998
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(98)90025-x
Subject(s) - metabolism , metabolic clearance rate , action (physics) , pharmacology , medicine , chemistry , pharmacokinetics , physics , quantum mechanics
Objectives 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 51 Cr‐ethylenediaminetetraacetic acid, 125 I‐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. Conclusion 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. Clinical Pharmacology & Therapeutics (1998) 64 , 73–86; doi: