Premium
Tolvaptan, an orally active non‐peptide arginine vasopressin V2 receptor antagonist, reduces ascites in rats with chronic liver injury
Author(s) -
Miyazaki Toshiki,
Fujiki Hiroyuki,
Yamamura Yoshitaka
Publication year - 2013
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12073
Subject(s) - tolvaptan , ascites , medicine , cirrhosis , vasopressin , diuretic , urology , gastroenterology , antagonist , endocrinology , pharmacology , receptor
Aim This is a non‐clinical, proof of concept study, showing that tolvaptan has efficacy in reducing ascites in chronic liver injury, using a rat model induced by repeated dimethylnitrosamine ( DMNA ) injection. Methods A rat model of chronic liver injury was induced by 10 mg/kg of repeated i.p. injection with DMNA for 6–9 weeks. Tolvaptan was administrated to rats that showed obvious and stable ascites, and abdominal circumference was evaluated as a surrogate marker of ascites volume. Rats were placed in metabolic cages with free access to food and water to collect urine over a 24‐h period. Results Oral tolvaptan (1 and 3 mg/kg) promoted a remarkable diuretic effect, decreasing bodyweight and abdominal circumference in a dose‐dependent manner. Plasma sodium concentration was increased by tolvaptan due to the large amount of free‐water excretion following tolvaptan administration. Conclusion Tolvaptan had therapeutic efficacy in the reduction of ascites in rats with chronic liver injury. These results are consistent with the clinical data showing tolvaptan has therapeutic implications in the reduction of ascites in patients with decompensated cirrhosis.