Orlandi Cesare, Zimmer Christopher A, Gheorghiade Mihai
Otsuka Maryland Research Institute, Clinical Development Department, 2440 Research Boulevard, Rockville, MD 20850 USA.
Future Cardiol. 2006 Nov;2(6):627-34. doi: 10.2217/14796678.2.6.627.
Tolvaptan is an oral, once-daily nonpeptide arginine vasopressin V(2)-receptor antagonist under development for the treatment of hyponatremia and congestive heart failure. In Phase II clinical trials, tolvaptan, in addition to standard therapy, increased fluid loss, resulting in decreased body weight and improved edema and serum sodium without affecting blood pressure, heart rate or renal function in patients with heart failure. The compound appeared to be well tolerated and dose-dependent adverse events were generally realated to its pharmacological activity, such as thirst and dry mouth. In patients with hyponatremia, tolvaptan appears to be more effective than fluid restriction at improving sodium levels without an increase in adverse events. An international Phase III outcome study; Efficacy of Vasopressin antagonism in hEaRt failurE outcome Study with Tolvaptan (EVEREST), evaluating the long-term efficacy and safety of tolvaptan in patients hospitalized with worsening heart failure, is currently ongoing.
托伐普坦是一种口服、每日一次的非肽类精氨酸加压素V(2)受体拮抗剂，目前正处于研发阶段，用于治疗低钠血症和充血性心力衰竭。在II期临床试验中，托伐普坦除标准治疗外，增加了液体丢失，导致体重减轻，水肿和血清钠改善，而不影响心力衰竭患者的血压、心率或肾功能。该化合物耐受性良好，剂量依赖性不良事件通常与其药理活性有关，如口渴和口干。在低钠血症患者中，托伐普坦在改善钠水平方面似乎比限液更有效，且不良事件没有增加。一项国际III期结局研究；托伐普坦治疗心力衰竭结局研究中加压素拮抗作用的疗效（EVEREST），正在评估托伐普坦对因心力衰竭恶化而住院患者的长期疗效和安全性。
