title: Phase III clinical pharmacology study of tolvaptan.
abstract: OBJECTIVE
  This study aimed to investigate the pharmacokinetics, pharmacodynamics, efficacy and safety of tolvaptan, an orally effective vasopressin V2-receptor antagonist.
  
  
  METHODS
  This was a multicenter, randomized, double-blind, parallel group study. Tolvaptan was administered at 7.5 or 15 mg, in combination with furosemide, for 7 days in Japanese heart failure (HF) patients with volume overload that had not resolved despite receiving furosemide.
  
  
  RESULTS
  The blood concentration of tolvaptan was maintained at a higher concentration for a longer time in patients who received 15 mg/day when compared with patients who received 7.5 mg/day. Tolvaptan increased urine volume and increased weight loss dose-dependently when used in combination with furosemide. Importantly, tolvaptan enhanced water diuresis without affecting blood electrolyte levels.
  
  
  CONCLUSIONS
  Tolvaptan exerts diuretic effects and causes body weight loss at the low dose of 7.5 mg; however, these effects were less than those elicited by 15 mg tolvaptan.
authors: Department of Cardio-Angiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minamiku, Sagamihara, Kanagawa, 252-0373, Japan. inotaka@med.kitasato-u.ac.jp
authors: Takayuki
authors: T
authors: Inomata
authors: Tohru
authors: T
authors: Izumi
authors: Masunori
authors: M
authors: Matsuzaki
authors: Masatsugu
authors: M
authors: Hori
authors: Atsushi
authors: A
authors: Hirayama
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D065092:Antidiuretic Hormone Receptor Antagonists; D044466:Asian People; D001552:Benzazepines / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000652:urine; D003404:Creatinine / Q000097:blood / Q000652:urine; D004232:Diuretics / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004489:Edema, Cardiac / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D006801:Humans; D008274:Magnesium / Q000652:urine; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood / Q000652:urine; D012964:Sodium / Q000097:blood / Q000652:urine; D000077602:Tolvaptan; D014527:Uric Acid / Q000652:urine
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D004232:Diuretics; D000077602:Tolvaptan; D014527:Uric Acid; D005665:Furosemide; D012964:Sodium; D003404:Creatinine; D008274:Magnesium; D011188:Potassium; D002118:Calcium