title: Aquaretic effect of lixivaptan, an oral, non-peptide, selective V2 receptor vasopressin antagonist, in New York Heart Association functional class II and III chronic heart failure patients.
abstract: OBJECTIVE
  The purpose of this study was to examine the renal effects of a V2 receptor arginine vasopressin (AVP) antagonist in heart failure.
  
  
  BACKGROUND
  Arginine vasopressin has been implicated in the renal water retention and dilutional hyponatremia associated with chronic heart failure.
  
  
  METHODS
  We examined the effects of the oral, non-peptide, selective V2 receptor antagonist lixivaptan in 42 diuretic-requiring patients with mild-to-moderate heart failure in a randomized, double-blind, placebo-controlled, ascending single-dose study. After overnight fluid deprivation, patients received single-blind placebo on day -1 (baseline) and double-blind study medication (placebo [n = 12] or lixivaptan 10, 30, 75, 150, 250, or 400 mg [n = 5 per dose group]) on day 1, followed by 4 h of continued fluid restriction and additional 20 h with ad libitum fluid intake.
  
  
  RESULTS
  At all but the 10-mg dose, lixivaptan produced a significant and dose-related increase in urine volume over 4 h, compared with placebo. During 24 h, increases in urine volume ranged from 1.8 l with placebo to 3.9 l after the 400-mg lixivaptan dose (p < 0.01). These increases in urine volumes were accompanied by significant increases in solute-free water excretion. At higher doses, serum sodium was significantly increased; AVP antagonism was well tolerated in these patients.
  
  
  CONCLUSIONS
  These observations confirm a role for AVP in the renal water retention associated with heart failure and suggest that the V2 receptor antagonist lixivaptan may be a promising therapeutic agent for the treatment of heart failure.
authors.affiliation: The Ohio State University Heart Center, Division of Cardiovascular Medicine, Columbus, Ohio 43210-1252, USA. abraham-1@medctr.osu.edu
authors.forename: William T
authors.initials: WT
authors.lastname: Abraham
authors.forename: Alireza A
authors.initials: AA
authors.lastname: Shamshirsaz
authors.forename: Kim
authors.initials: K
authors.lastname: McFann
authors.forename: Ron M
authors.initials: RM
authors.lastname: Oren
authors.forename: Robert W
authors.initials: RW
authors.lastname: Schrier
mesh_terms: D000284:Administration, Oral; D065092:Antidiuretic Hormone Receptor Antagonists; D002303:Cardiac Output, Low / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology* / Q000652:urine; D002908:Chronic Disease; D004231:Diuresis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004573:Electrolytes / Q000097:blood; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D012720:Severity of Illness Index; D012964:Sodium / Q000097:blood; D014667:Vasopressins / Q000097:blood
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D004573:Electrolytes; D006728:Hormones; D014667:Vasopressins; D012964:Sodium