Zeltser David, Rosansky Steven, van Rensburg Hannes, Verbalis Joseph G, Smith Neila
Department of Internal Medicine D, Sourasky Medical Center, Tel Aviv, Israel.
Am J Nephrol. 2007;27(5):447-57. doi: 10.1159/000106456. Epub 2007 Jul 26.
Most cases of hyponatremia--serum sodium concentration ([Na+]) < 135 mEq/l (< 135 mM)--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.
Eighty-four hospitalized patients with euvolemic or hypervolemic hyponatremia (serum [Na+] 115 to < 130 mEq/l) were randomly assigned to receive intravenous placebo or conivaptan administered as a 30-min, 20-mg loading dose followed by a 96-hour infusion of either 40 or 80 mg/day. The primary efficacy measure was change in serum [Na+], measured by the baseline-adjusted area under the [Na+]-time curve. The secondary measures included time from first dose to a confirmed > or = 4 mEq/l serum [Na+] increase, total time patients had serum [Na+] > or = 4 mEq/l higher than baseline, change in serum [Na+] from baseline to the end of treatment, and number of patients with a confirmed > or = 6 mEq/l increase in serum [Na+] or normal [Na+] (> or = 135 mEq/l).
Both conivaptan doses increased area under the [Na+]-time curve during the 4-day treatment (p < 0.0001 vs. placebo). From baseline to the end of treatment, the least-squares mean +/- standard error serum [Na+] 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 < 0.001 vs. placebo, both doses). Conivaptan was generally well tolerated, although infusion-site reactions led to the withdrawal of 1 (3%) and 4 (15%) of patients given conivaptan 40 and 80 mg/day, respectively.
Among patients with euvolemic or hypervolemic hyponatremia, 4-day intravenous infusion of conivaptan 40 mg/day significantly increased serum [Na+] and was well tolerated.
大多数低钠血症病例——血清钠浓度（[Na⁺]）<135 mEq/L（<135 mM）——与血浆精氨酸加压素水平升高有关。本研究调查了血管加压素V1A/V2受体拮抗剂静脉注射考尼伐坦（YM087）治疗等容性和高容性低钠血症的疗效和耐受性。
84例住院的等容性或高容性低钠血症患者（血清[Na⁺]为115至<130 mEq/L）被随机分配接受静脉注射安慰剂或考尼伐坦，先给予30分钟20毫克的负荷剂量，然后以40或80毫克/天的剂量进行96小时输注。主要疗效指标是血清[Na⁺]的变化，通过[Na⁺]-时间曲线下经基线调整的面积来测量。次要指标包括从首次给药到确认血清[Na⁺]升高≥4 mEq/L的时间、患者血清[Na⁺]比基线高≥4 mEq/L的总时间、从基线到治疗结束时血清[Na⁺]的变化，以及确认血清[Na⁺]升高≥6 mEq/L或血清[Na⁺]正常（≥135 mEq/L）的患者数量。
在4天的治疗期间，考尼伐坦的两个剂量均增加了[Na⁺]-时间曲线下的面积（与安慰剂相比，p<0.0001）。从基线到治疗结束，与安慰剂相关的血清[Na⁺]升高的最小二乘均值±标准误为0.8±0.8 mEq/L；考尼伐坦40毫克/天组为6.3±0.7 mEq/L；考尼伐坦80毫克/天组为9.4±0.8 mEq/L。考尼伐坦显著改善了所有次要疗效指标（与安慰剂相比，两个剂量组p均<0.001）。考尼伐坦总体耐受性良好，尽管输注部位反应导致分别有1例（3%）接受40毫克/天考尼伐坦治疗的患者和4例（15%）接受80毫克/天考尼伐坦治疗的患者退出研究。
在等容性或高容性低钠血症患者中，4天静脉输注40毫克/天的考尼伐坦可显著提高血清[Na⁺]水平，且耐受性良好。
