title: Can serum albumin level affect the pharmacological action of tolvaptan in patients with liver cirrhosis? A post hoc analysis of previous clinical trials in Japan.
abstract: BACKGROUND
  Patients with hypoalbuminemia often fail to respond to increased doses of loop diuretics. We therefore performed a post hoc analysis to investigate the pharmacological action of tolvaptan and whether it is dependent on the serum albumin level.
  
  
  METHODS
  This analysis was based on four previous clinical trials of tolvaptan in patients with liver cirrhosis who exhibited insufficient response to conventional diuretics. We analyzed the correlation between the change in the initial 24-h cumulative urine volume from baseline and the serum albumin level at baseline, and assessed potential predictive factors of response to tolvaptan.
  
  
  RESULTS
  The correlation coefficient was 0.029 in the placebo group and -0.112 in the 7.5 mg tolvaptan group of patients with liver cirrhosis. Administration of tolvaptan provoked a stable response regardless of the serum albumin level. Tolvaptan use was identified as a significant predictor of pharmacological action, and was shown to change the initial urine volume by 885 mL (P < 0.0001) in liver cirrhosis patients.
  
  
  CONCLUSIONS
  In this post hoc analysis, tolvaptan increased the initial urine volume from baseline regardless of serum albumin levels. Use of tolvaptan as an add-on therapy to loop diuretics can be considered an optimal therapeutic option in patients with insufficient response to loop diuretics.
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi, 755-8505, Japan. sakaida@yamaguchi-u.ac.jp.
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
authors.affiliation: Department of Medical Affairs, Otsuka Pharmaceutical Co. Ltd., Tokyo, Japan. nakajimak@otsuka.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Shunan Memorial Hospital, Kudamatsu, Yamaguchi, Japan.
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Okita
authors.affiliation: Osaka Medical Center for Cancer and Cardiovascular Diseases President Emeritus, Osaka, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
authors.affiliation: Kitasato University, Sagamihara, Kanagawa, Japan.|Kojinkai Niigata Minami Hospital, Niigata, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Izumi
authors.affiliation: Department of Medical Affairs, Otsuka Pharmaceutical Co. Ltd., Tokyo, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Sakurai
authors.affiliation: Department of Medical Affairs, Otsuka Pharmaceutical Co. Ltd., Tokyo, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Shibasaki
authors.affiliation: Department of Medical Affairs, Otsuka Pharmaceutical Co. Ltd., Tokyo, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Tachikawa
authors.affiliation: Department of Medical Affairs, Otsuka Pharmaceutical Co. Ltd., Tokyo, Japan.
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Tsubouchi
authors.affiliation: Department of Medical Affairs, Otsuka Pharmaceutical Co. Ltd., Tokyo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Oka
authors.affiliation: Department of Medical Affairs, Otsuka Pharmaceutical Co. Ltd., Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use; D001552:Benzazepines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007010:Hyponatremia; D007564:Japan / Q000453:epidemiology; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D018570:Risk Assessment / Q000379:methods*; D012709:Serum Albumin / Q000378:metabolism*; D015996:Survival Rate / Q000639:trends; D000077602:Tolvaptan
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D012709:Serum Albumin; D000077602:Tolvaptan
keywords: Albumin; Diuretics; Initial urine volume; Liver cirrhosis; Tolvaptan