Successful long-term treatment of hyponatremia in syndrome of inappropriate antidiuretic hormone secretion with satavaptan (SR121463B), an orally active nonpeptide vasopressin V2-receptor antagonist.
The effects of satavaptan (SR121463B), a novel long-acting orally active vasopressin V(2)-receptor antagonist, were investigated in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). In the first part of this randomized, double-blind study, 34 patients first were treated with satavaptan (versus placebo) for up to 5 d and then during 23 d of open-label dosage-adjustment period. In the second part of the study, long-term efficacy and safety of satavaptan was assessed in an open-label trial during at least 12 mo. Mean (+/-SD) serum sodium (SNa) levels before treatment were 127 +/- 2 mmol/L (placebo, n = 8), 125 +/- 6 mmol/L (25 mg, n = 14), and 127 +/- 5 mmol/L (50 mg, n = 12). Responders (patients SNa levels normalized or increased by at least 5 mmol/L from baseline during the double-blind period) were 79% in the 25-mg group (SNa 136 +/- 3 mmol/L; P = 0.006), 83% in the 50-mg group (SNa 140 +/- 6 mmol/L; P = 0.005), and 13% in the placebo group (SNa 130 +/- 5 mmol/L). No drug-related serious adverse events were recorded. During the long-term treatment, 15 of 18 enrolled patients achieved 6 mo and 10 achieved 12 mo of treatment. The SNa response was maintained during this time with a good tolerance. The new oral vasopressin V(2)-receptor antagonist satavaptan adequately corrects mild or moderate hyponatremia in patients with SIADH and has a good safety profile.
Soupart
Alain
A
Department of Internal Medicine, Jolimont/Tubize-Nivelles Hospital, Tubize, Belgium. alainsoupart@swing.be
Gross
Peter
P
Legros
Jean-Jacques
JJ
Alföldi
Sándor
S
Annane
Djillali
D
Heshmati
Hassan M
HM
Decaux
Guy
G
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists; D001834:Body Water / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007010:Hyponatremia / Q000188:drug therapy* / Q000209:etiology; D007177:Inappropriate ADH Syndrome / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000627:therapeutic use*; D010919:Placebos; D012964:Sodium / Q000097:blood / Q000652:urine; D013141:Spiro Compounds / Q000627:therapeutic use*
D065092:Antidiuretic Hormone Receptor Antagonists; D009025:Morpholines; D010919:Placebos; D013141:Spiro Compounds; D012964:Sodium; C103281:satavaptan