VPA-985 is an orally active, competitive
vasopressin V(2) receptor antagonist that in normal human beings increases water excretion without affecting solute excretion. Whether solute excretion is affected in patients with
hyponatremia resulting from inappropriate secretion of
antidiuretic hormone (
SIADH) or from
cirrhosis treated with
VPA-985 is unknown. Six hyponatremic patients with
SIADH and 5 hyponatremic patients with
cirrhosis with ascitis (CWAs) were treated with 50 or 100 mg
VPA-985 twice daily. Evolution of
creatinine,
urea,
uric acid,
sodium,
potassium, and osmotic clearance were determined. Volume
hormones (plasma
renin [PR],
aldosterone,
antidiuretic hormone [ADH],
atrial natriuretic factor [
ANF]) were also determined before and
after treatment. In patients with
SIADH, serum
sodium concentration (SNa) was 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
sodium 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 diuresis (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 H(2)O to 209 +/- 55 mOsm/kg H(2)O. 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
sodium excretion (from 23 +/- 18 mmol/24 hours to 65 6 60 mmol/24 hours the second day of VPA administration). The higher
sodium excretion was also connected 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. Urine osmolality decreased from 509 +/- 142 mOsm/kg H(2)O before VPA to 194 +/- 106 mOsm/kg H(2)O 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 did not change.
VPA-985 is a highly effective
drug in the short-term management of hyponatremic patients with
SIADH or CWAs. SNa correction is associated with urinary
sodium retention in
SIADH, whereas in CWAs a mild increase in
sodium excretion is observed.