Aquaretic effects of niravoline, a kappa-opioid agonist, in patients with cirrhosis

Background/Aims: In patients with cirrhosis, decreased renal water excretio n is a common complication. Niravoline (RU51599), a kappa-opioid receptor a gonist, has been shown to induce an aquaretic response. The aim of this stu dy was to evaluate the aquaretic effect and tolerance of niravoline in pati ents with cirrhosis. Methods: Biochemical tests and hemodynamic values were determined before an d 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 o smolality significantly decreased at 2 h (from 290+/-4 to 286+/-4 mOsm/kg), Plasma sodiun concentrations increased significantly at 3 h (from 133+/-1 to 134+/-1 mEq/l), Heart rate and arterial pressure did not change. The hig hest doses (1.5 mg or 2 mg) induced personality disorders and mild confusio n within 2 h, These effects reversed completely within 8 h. Conclusion: This study shows that niravoline administration induces an aqua retic response and is well tolerated, at moderate doses, in patients with c irrhosis, Thus, moderate doses of niravoline may be useful for treating pat ients with cirrhosis and water retention.