Acute Aquaresis by the Nonpeptide Arginine Vasopressin (AVP) Antagonist OPC-31260 Improves Hyponatremia in Patients with Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH)
Toshikazu Saito,
San-e Ishikawa,
Keishi Abe,
Kyuzi Kamoi,
Kenichi Yamada,
Kurakazu Shimizu,
Takao Saruta and
Sho Yoshida
Department of Medicine (To. S., S.I.), Jichi Medical School,
Tochigi; Second Department of Medicine (K.A.), Tohoku University School
of Medicine, Sendai; Department of Medicine (K.K.), Nagaoka Red Cross
Hospital, Nagaoka; Department of Medicine (K.Y.), National Sakura
Hospital, Sakura; Department of Medicine (K.S.), Tokyo Rosai Hospital,
Tokyo; Department of Medicine (Ta. S.), Keio University School of
Medicine, Tokyo; Second Department of Medicine (S.Y.), Chiba University
School of Medicine, Chiba, Japan
Address all correspondence and requests for reprints to: Toshikazu Saito, M.D., Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical School, 3311-1 Yakushiji Minamikawachi, Tochigi 329-04 Japan.
The present study was undertaken to determine whether the nonpeptide
V2arginine vasopressin (AVP) antagonist
5-dimethylamino-1[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine
hydrochloride(OPC-31260) produces water diuresis and improves
hyponatremiain patients with the syndrome of inappropriate secretion
ofantidiuretic 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 intervalsduring the
6 h observation period each day. A single administrationof 0.25
and 0.5 mg/kg OPC-31260 increased the 4 h cumulativeurine volume
and decreased urinary osmolality to below 225 mOsm/kgH2O.
Such a diuretic effect was independent of an increase inurinary solute
excretions. This aquaresis by 0.5 mg/kg OPC-31260caused a significant
increase in serum sodium level by approximately3 mEq/L. The
antagonistic effect of OPC-31260 lasted for 4 hwhen it was given
intravenously. These results indicate thatOPC-31260 is an effective
therapeutic agent for hyponatremiain patients with SIADH.
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