title: Predictive factors of the pharmacological action of tolvaptan in patients with liver cirrhosis: a post hoc analysis.
abstract: BACKGROUND
  Tolvaptan has been approved in Japan for the treatment of hepatic edema. An important consideration in providing a clinical benefit to patients with liver cirrhosis is the improvement of ascites-related clinical symptoms. In the present post hoc analysis, we aimed to identify factors that were predictive of the potency of tolvaptan, and to examine the relationship between changes in initial urine volume and improvement in ascites-related clinical symptoms.
  
  
  METHODS
  This post hoc analysis was based on three previous phase 2 and 3 clinical trials of tolvaptan in patients with liver cirrhosis. Predictive factors associated with a change in initial urine volume were identified. A change of ≥500 mL from baseline confirmed the pharmacological action of tolvaptan treatment. The relationship between the change in initial urine volume and improvement in ascites-related clinical symptoms was also examined.
  
  
  RESULTS
  A total of 152 patients were enrolled in this study. Body weight and BUN were identified as predictive parameters. Among patients with a change in initial urine volume of ≥500 mL, 75 % demonstrated improvement in ascites-related clinical symptoms, while no improvement was seen in those with a change of <500 mL. None of the patients with initial urine volume of <500 mL showed resolution of symptoms.
  
  
  CONCLUSIONS
  Change in urine volume was affected by both baseline body weight and BUN in tolvaptan-treated subjects. Higher urine output was associated with improvements in ascites-related clinical symptoms.
authors.affiliation: Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan. sakaida@yamaguchi-u.ac.jp.
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
authors.affiliation: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Terai
authors.affiliation: Department of Medical Affairs, Otsuka Pharmaceutical Co., Ltd., 2-16-4 Konan, Minato-ku, Tokyo, 108-8242, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Department of Medical Affairs, Otsuka Pharmaceutical Co., Ltd., 2-16-4 Konan, Minato-ku, Tokyo, 108-8242, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Shibasaki
authors.affiliation: Department of Medical Affairs, Otsuka Pharmaceutical Co., Ltd., 2-16-4 Konan, Minato-ku, Tokyo, 108-8242, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Tachikawa
authors.affiliation: Department of Medical Affairs, Otsuka Pharmaceutical Co., Ltd., 2-16-4 Konan, Minato-ku, Tokyo, 108-8242, Japan.
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Tsubouchi
mesh_terms: D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D001201:Ascites / Q000188:drug therapy* / Q000473:pathology; D001552:Benzazepines / Q000494:pharmacology / Q000627:therapeutic use*; D001806:Blood Urea Nitrogen; D001835:Body Weight; D005260:Female; D006801:Humans; D007564:Japan; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D000077602:Tolvaptan; D014556:Urine
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D000077602:Tolvaptan
keywords: Ascites-related clinical symptom; Initial urine volume; Liver cirrhosis; Predictive factor; Tolvaptan