Combined effects of vasopressin V2 receptor antagonist and loop diuretic in humans

Aims: 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 V-2 receptor antagonist OPC-31260, an aquaretic, and furosemide, a saluretic, on free water excretion and serum sodium concentration (P-Na), Material and 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 (0), 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/kgH(2)O) as a result of an additive increase in maximal urine volume (F: 7.7 +/- 1.9, 0: 6.8 +/- 0.5, O+F: 13.2 +/- 1.4 ml/min) with increased electrolyte-free water excretion (F: 0.35 +/- 0.5, O:5.3 +/- 0.5, O+F: 4.8 +/- 0.5 ml/min) while maintaining sodium excretion (F: 731 +/- 110, O+F: 1,064 +/- 149 Eq/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.