Aquaretic effects of niravoline, a kappa-opioid agonist, in patients with cirrhosis.
OBJECTIVE
In patients with cirrhosis, decreased renal water excretion is a common complication. Niravoline (RU51599), a kappa-opioid receptor agonist, has been shown to induce an aquaretic response. The aim of this study was to evaluate the aquaretic effect and tolerance of niravoline in patients with cirrhosis.


METHODS
Biochemical tests and hemodynamic values were determined before and 1, 2, 3 and 24 h after niravoline administration at doses ranging from 0.5 to 2 mg iv in 18 patients with cirrhosis.


RESULTS
Diuresis significantly increased in the first hour from 64+/-9 to 146+/-31 ml/h, and returned to basal values after 3 h. Free water clearance also significantly increased, reaching the positive range at 1 h. Plasma osmolality significantly decreased at 2 h (from 290+/-4 to 286+/-4 mOsm/kg). Plasma sodium concentrations increased significantly at 3 h (from 133+/-1 to 134+/-1 mEq/l). Heart rate and arterial pressure did not change. The highest doses (1.5 mg or 2 mg) induced personality disorders and mild confusion within 2 h. These effects reversed completely within 8 h.


CONCLUSIONS
This study shows that niravoline administration induces an aquaretic response and is well tolerated, at moderate doses, in patients with cirrhosis. Thus, moderate doses of niravoline may be useful for treating patients with cirrhosis and water retention.
Gadano
A
A
Laboratoire d'Hémodynamique Splanchnique et de Biologie Vasculaire INSERMU-481 and Service d'Hepatologie, Hôpital Beaujon, Clichy, France.
Moreau
R
R
Pessione
F
F
Trombino
C
C
Giuily
N
N
Sinnassamy
P
P
Valla
D
D
Lebrec
D
D
D044482:Benzeneacetamides; D001834:Body Water / Q000187:drug effects / Q000378:metabolism; D004231:Diuresis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007010:Hyponatremia; D007275:Injections, Intravenous; D008103:Liver Cirrhosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines / Q000627:therapeutic use*; D017473:Receptors, Opioid, kappa / Q000819:agonists*
D044482:Benzeneacetamides; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C100946:niravoline