title: Combined effects of vasopressin V2 receptor antagonist and loop diuretic in humans.
abstract: OBJECTIVE
  Patients with edematous diseases are generally treated with diuretics, but frequently present with hyponatremia associated with impaired water excretion. This study investigated the combined effects of vasopressin V2 receptor antagonist OPC-31260, an aquaretic, and furosemide, a saluretic, on free water excretion and serum sodium concentration (PNa).
  
  
  METHODS
  The study was planned as an open-label, 4-period, 4-treatment, crossover study in 12 healthy subjects using single doses of placebo, furosemide 20 mg (F), OPC-31260 30 mg (O), and furosemide 20 mg plus OPC-31260 30 mg (O+F).
  
  
  RESULTS
  OPC-31260 co-administered with furosemide induced an increase in PNa and serum osmolality (F: 281.6 +/- 0.7, O+F: 284.9 +/- 0.7 mOsm/kgH2O) as a result of an additive increase in maximal urine volume (F: 7.7 +/- 1.9, O: 6.8 4 0.5, O+F: 13.2 +/- 1.4 ml/min) with increased electrolyte-free water excretion (F: 0.35 +/- 0.15, O: 5.3 4 0.5, O+F: 4.8 +/- 0.5 ml/min) while maintaining sodium excretion (F: 731 +/- 110, O+F: 1,064 +/- 149 microEq/min). It was suggested that by the co-administration, the resulting decreased generation of free water in Henle's loop was canceled out by a decrease in back--diffusion of free water across the collecting ducts.
  
  
  CONCLUSIONS
  The co-administration may be particularly effective in treating edema and hyponatremia in edematous diseases.
authors.affiliation: Sumiyoshi Clinic Hospital, Mito, Ibaraki, Japan. aquamoon@mui.biglobe.ne.jp
authors.forename: K
authors.initials: K
authors.lastname: Shimizu
mesh_terms: D000328:Adult; D001552:Benzazepines / Q000494:pharmacology*; D018592:Cross-Over Studies; D004232:Diuretics / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004487:Edema / Q000188:drug therapy; D004573:Electrolytes / Q000652:urine; D005665:Furosemide / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007010:Hyponatremia / Q000188:drug therapy; D008297:Male; D009994:Osmolar Concentration; D011188:Potassium / Q000652:urine*; D012044:Regression Analysis; D012083:Renin / Q000652:urine; D012964:Sodium / Q000097:blood* / Q000652:urine; D014554:Urination / Q000502:physiology; D014867:Water / Q000378:metabolism
chemical_list: D001552:Benzazepines; D004232:Diuretics; D004573:Electrolytes; D014867:Water; C076251:mozavaptan; D005665:Furosemide; D012964:Sodium; D012083:Renin; D011188:Potassium