title: The pharmacokinetics and pharmacodynamics of tolvaptan in patients with liver cirrhosis with insufficient response to conventional diuretics: a multicentre, double-blind, parallel-group, phase III study.
abstract: OBJECTIVE
  This study investigated the pharmacokinetic and pharmacodynamic profile of tolvaptan, and verified its efficacy and safety in patients with liver cirrhosis-associated ascites, with insufficient response to conventional diuretic treatment.
  
  
  METHODS
  This multicentre, double-blind, parallel-group study allocated patients with cirrhosis to receive either 3.75 or 7.5 mg/day tolvaptan orally, once daily, for 7 days. Pharmacokinetic, pharmacodynamic and efficacy variables were measured.
  
  
  RESULTS
  Tolvaptan was shown to have high plasma concentrations, and prolonged duration of maximum concentration and half life, in these patients with impaired hepatic function. Tolvaptan resulted in dose-dependent decreases in body weight and ascites volume, and increases in urine output. There were no effects on urinary or serum electrolytes. Tolvaptan was well tolerated, with a good safety profile.
  
  
  CONCLUSIONS
  Tolvaptan at 3.75 mg/day exerts some effects due to the pharmacokinetic profile in patients with liver cirrhosis. Tolvaptan at 7.5 mg/day is a clinically useful option for treating patients who do not respond well to conventional diuretics.
authors: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan. sakaida@yamaguchi-u.ac.jp
authors: I
authors: I
authors: Sakaida
authors: M
authors: M
authors: Yanase
authors: Y
authors: Y
authors: Kobayashi
authors: T
authors: T
authors: Yasutake
authors: M
authors: M
authors: Okada
authors: K
authors: K
authors: Okita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D065092:Antidiuretic Hormone Receptor Antagonists; D001201:Ascites / Q000188:drug therapy; D001552:Benzazepines / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D004232:Diuretics / Q000627:therapeutic use; D004311:Double-Blind Method; D004573:Electrolytes / Q000097:blood / Q000652:urine; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000077602:Tolvaptan
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D004232:Diuretics; D004573:Electrolytes; D000077602:Tolvaptan