Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia.

Background: Most cases of hyponatremia – serum sodium concentration ([Na+]) M) – are associated with an elevated plasma arginine vasopressin level. This study investigated the efficacy and tolerability of intravenous conivaptan (YM087), a vasopressin V1A/V2-receptor antagonist, in treating euvolemic and hypervolemic hyponatremia. Methods: Eighty-four hospitalized patients with euvolemic or hypervolemic hyponatremia (serum [Na+] 115 to +], measured by the baseline-adjusted area under the [Na+]-time curve. The secondary measures included time from first dose to a confirmed ≧4 mEq/l serum [Na+] increase, total time patients had serum [Na+] ≧4 mEq/l higher than baseline, change in serum [Na+] from baseline to the end of treatment, and number of patients with a confirmed ≧6 mEq/l increase in serum [Na+] or normal [Na+] (≧135 mEq/l). Results: Both conivaptan doses increased area under the [Na+]-time curve during the 4-day treatment (p +] increase associated with placebo was 0.8 ± 0.8 mEq/l; with conivaptan 40 mg/day, 6.3 ± 0.7 mEq/l; and with conivaptan 80 mg/day, 9.4 ± 0.8 mEq/l. Conivaptan significantly improved all secondary efficacy measures (p Conclusion: Among patients with euvolemic or hypervolemic hyponatremia, 4-day intravenous infusion of conivaptan 40 mg/day significantly increased serum [Na+] and was well tolerated.