ACUTE AQUARESIS BY THE NONPEPTIDE ARGININE-VASOPRESSIN (AVP) ANTAGONIST OPC-31260 IMPROVES HYPONATREMIA IN PATIENTS WITH SYNDROME OF INAPPROPRIATE SECRETION OF ANTIDIURETIC-HORMONE (SIADH)

The present study was undertaken to determine whether the nonpeptide V -2 arginine vasopressin (AVP) antagonist ylamino)benzoyl]-2,3,4,5-tetr ahydro-1H-benzazepine hydrochloride (OPC-31260) produces water diuresi s and improves hyponatremia in patients with the syndrome of inappropr iate secretion of antidiuretic hormone (SIADH). Eleven patients (9 mal es and 2 females, 64 +/- 3.5 yr) with SIADH were included in the prese nt protocol, which was comprised of 3 successive days. Day 1 was a con trol day, and on days 2 and 3 OPC-31260 was administered intravenously . Five blood and urine collections were made at 1-2 h intervals during the 6 h observation period each day. A single administration of 0.25 and 0.5 mg/kg OPC-31260 increased the 4 h cumulative urine volume and decreased urinary osmolality to below 225 mOsm/kg H2O. Such a diuretic effect was independent of an increase in urinary solute excretions. T his aquaresis by 0.5 mg/kg OPC-31260 caused a significant increase in serum sodium level by approximately 3 mEq/L. The antagonistic effect o f OPC-31260 lasted for 4 h when it was given intravenously. These resu lts indicate that OPC-31260 is an effective therapeutic agent for hypo natremia in patients with SIADH.