Difference in solute excretion during correction of hyponatremic patients with cirrhosis or syndrome of inappropriate secretion of antidiuretic hormone by oral vasopressin V-2 receptor antagonist VPA-985

VPA-985 is an orally active, competitive vasopressin Vp receptor antagonist that On normal human beings increases water excretion without affecting so lute excretion. Whether solute excretion is affected in patients with hypon atremia resulting from inappropriate secretion of antidiuretic hormone (SIA DH) or from cirrhosis treated with VPA-985 is unknown. Six hyponatremic pat ients with SIADH and 5 hyponatremic patients with cirrhosis with ascitis (C WAs) were treated with 50 or 100 mg VPA-985 twice daily. Evolution of creat inine, urea, uric acid, sodium, potassium, and osmotic clearance were deter mined. Volume hormones (plasma renin (PR), aldosterone, antidiuretic hormon e (ADH), atrial natriuretic factor (ANF)) were also determined before and a fter treatment. In patients with SIADH, serum sodium concentration (SNa) wa s generally corrected in 1 day (SNa: 126 +/- 4.5 mmol/L at t = 0 hours and 133 +/- 5.6 mmol/L at t = 24 hours) and associated with a decrease in sodiu m excretion (from 82 +/- 22 mmol/24 hours to 45 +/- 21 mmol/24 hours; P < 0 .05) without modification in potassium excretion. Despite an increase in di uresis (from 0.84 +/- 0.2 ml/min to 1.46 +/- 0.4 ml/min) urea and uric acid clearances decreased. Urine osmolality decreased from 414 +/- 148 mOsm/kg H2O to 209 +/- 55 mOsm/kg H2O. Volume hormones did not change. In the CWAs the rise of SNa was more progressive (SNa: 126 +/- 2.8 mmol/L at t = H0 to 133 +/- 4.9 mmol/L at t = 48 hours) and parallel to an augmentation in sodi um excretion (from 23 +/- 18 mmol/24 hours to 65 6 60 mmol/24 hours the sec ond day of VPA administration). The higher sodium excretion was also connec ted with a progression in potassium excretion (from 22 6 7 mmol/24 hours to 36 +/- 18 mmol/24 hours). The increase in diuresis under VPA from 0.42 +/- 0.2 ml/min to 1.7 +/- 0.9 ml/min resulted in a higher urea clearance. Urin e osmolality decreased from 509 +/- 142 mOsm/kg H2O before VPA to 194 +/- 1 06 mOsm/kg H2O after VPA. ADH increased in CWAs treated with VPA, from 1.9 +/- 1.2 pg/mL to 5.3 +/- 2.8 pg/mL (P < .05) while other volume hormones di d not change. VPA-985 is a highly effective drug in the short-term manageme nt of hyponatremic patients with SIADH or CWAs. SNa correction is associate d with urinary sodium retention in SIADH, whereas in CWAs a mild increase i n sodium excretion is observed.