Tolvaptan, an orally active non-peptide arginine vasopressin V2 receptor antagonist, reduces ascites in rats with chronic liver injury

Authors


  • Conflict of interest: All authors are employees of Otsuka Pharmaceutical, which is developing tolvaptan.

Abstract

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.

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