Aquaretic effect of lixivaptan, an oral, non-peptide, selective V2 receptor vasopressin antagonist, in New York Heart Association functional class II and III chronic heart failure patients

Journal of the American College of Cardiology
William T AbrahamRobert W Schrier

Abstract

The purpose of this study was to examine the renal effects of a V2 receptor arginine vasopressin (AVP) antagonist in heart failure. Arginine vasopressin has been implicated in the renal water retention and dilutional hyponatremia associated with chronic heart failure. We examined the effects of the oral, non-peptide, selective V2 receptor antagonist lixivaptan in 42 diuretic-requiring patients with mild-to-moderate heart failure in a randomized, double-blind, placebo-controlled, ascending single-dose study. After overnight fluid deprivation, patients received single-blind placebo on day -1 (baseline) and double-blind study medication (placebo [n = 12] or lixivaptan 10, 30, 75, 150, 250, or 400 mg [n = 5 per dose group]) on day 1, followed by 4 h of continued fluid restriction and additional 20 h with ad libitum fluid intake. At all but the 10-mg dose, lixivaptan produced a significant and dose-related increase in urine volume over 4 h, compared with placebo. During 24 h, increases in urine volume ranged from 1.8 l with placebo to 3.9 l after the 400-mg lixivaptan dose (p < 0.01). These increases in urine volumes were accompanied by significant increases in solute-free water excretion. At higher doses, serum sodium was significa...Continue Reading

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