The bradykinin antagonist icatibant increases electrolyte and water excretion after sodium challenge in patients with liver cirrhosis

• Published in: Clinical pharmacology and therapeutics 2004-02, Vol.75 (2), p.P12-P12
• Main Authors: Russmann, S., Decosterd, L., Buclin, T., Schwaar, T., Baumann, S., Brunner‐Ferber, F., Rosenkranz, B., Knolle, J., Reichen, J.
• Format: Article
• Language: English
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1016/j.clpt.2003.11.043

Purpose Patients with hepatic insufficiency are known to cope less efficiently with Na load. In a rat CCl4‐induced liver cirrhosis model, Icatibant, a potent bradykinin‐2 receptor antagonist, prevented Na retention, improved diuresis, and reduced microvascular leakage (Wirth et al Eur J Pharmacol 1997; 37: 45–53). Methods: In a randomized, double‐blind, proof‐of‐concept study, 8 patients with liver cirrhosis (Child Pugh score 5‐8) and 8 healthy subjects on standardized diet received a constant 3 day infusion of Icatibant (0.15 mg/kg/day) or vehicle (placebo), with Na load on Day 2 (2L NaCl 0.9% i.v.). Results: Using sinistrine clearance, renal function did not change during treatment while the baseline extracellular body water (Vd) was higher in patients than volunteers (12.4 vs. 10.2 L/m2, p=0.05). In patients, 6‐12h after NaCl load, Icatibant increased Na excretion vs. placebo by 6.9 mmol/h (p=0.02), K excretion by 1.24 mmol/h (p=0.04), urine osmolarity by 18.54 mmol/h (p=0.01), and urine flow by 41.4 mL/h (p=0.05) while on Day 3 cumulative Na excretion was higher (+85.9 mmol, p=0.09) and body weight lower (−0.53 kg, p=0.04). In volunteers, response to Na load was prompt and nearly similar for both periods. Icatibant was safe and well tolerated. Conclusion: Icatibant increases the natriuretic response in cirrhotic patients after Na load. Its potential for treating patients with refractory ascites should be investigated further. Clinical Pharmacology & Therapeutics (2004) 75, P12–P12; doi: 10.1016/j.clpt.2003.11.043