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 non-peptide V2 arginine vasopressin (AVP) antagonist 5-dimethylamino- 1[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepi ne hydrochloride (OPC-31260) produces water diuresis and improves hyponatremia in patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Eleven patients (9 males and 2 females, 64 +/- 3.5 yr) with SIADH were included in the present protocol, which was comprised of 3 successive days. Day 1 was a control 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. This aquaresis by 0.5 mg/kg OPC-31260 caused a significant increase in serum sodium level by approximately 3 mEq/L. The antagonistic effect of OPC-31260 lasted for 4 h when it was given intravenously. These results indicate that OPC-31260 is an effective therapeutic agent for hyponatremia in patients with SIADH.
Saito
T
T
Department of Medicine, Jichi Medical School, Tochigi, Japan.
Ishikawa
S
S
Abe
K
K
Kamoi
K
K
Yamada
K
K
Shimizu
K
K
Saruta
T
T
Yoshida
S
S
D000368:Aged; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors*; D001552:Benzazepines / Q000627:therapeutic use*; D004231:Diuresis; D004232:Diuretics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007010:Hyponatremia / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D007177:Inappropriate ADH Syndrome / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D012964:Sodium / Q000097:blood; D016896:Treatment Outcome; D014556:Urine / Q000737:chemistry
D001552:Benzazepines; D004232:Diuretics; D001127:Arginine Vasopressin; C076251:mozavaptan; D012964:Sodium