Aperis Georgios, Alivanis Polichronis
Department of Nephrology, General Hospital of Rhodes, Greece.
Rev Recent Clin Trials. 2011 May;6(2):177-88. doi: 10.2174/157488711795177895.
Tolvaptan is a new agent in the treatment of normovolemic and hypervolemic hyponatremia. It is a V(2) receptor antagonist inducing free water diuresis. It has been recently approved in USA and Europe for the treatment of hyponatremia associated with SIADH, cirrhosis as well as heart failure, while in hypovolemic hyponatremia its use is contraindicated. The drug also appears to be effective in the acute exacerbations of heart failure that need hospitalization. In the short-term tolvaptan seems to relieve acute congestive symptoms and improves mortality. However, the long-term effects on mortality are still controversial. The favorable short-term effects are ascribed to the selective V(2) receptor blocking, while the unopposed stimulation of V(1A) may give an explanation for the lack of long-term benefit. The drug should be initiated in the hospital setting because careful monitoring of fluid balance is recommended. It is administered orally giving the advantage of continuation in the outpatient setting. Moreover tolvaptan may have a role in the treatment of autosomal dominant polycystic kidney disease (ADPKD). Its effectiveness has been shown in animal models and Phase 3 clinical trial as well as an open-label study is now active. Since tolvaptan is metabolized by the cytochrome CYP3A4 in the liver physicians should be aware of possible drug to drug interactions. Resulting from large studies tolvaptan appears well tolerated. Common side effects are thirst, dry mouth and polyuria. Tolvaptan opens a new page not only in the treatment of normovolemic and hypervolemic hyponatremia but also in the treatment of acute decompensated heart failure and probably in ADPKD.
托伐普坦是治疗等容性和高容性低钠血症的一种新药。它是一种V(2)受体拮抗剂，可诱导自由水利尿。最近它在美国和欧洲已被批准用于治疗与抗利尿激素分泌异常综合征（SIADH）、肝硬化以及心力衰竭相关的低钠血症，而在低容性低钠血症中禁止使用。该药物在需要住院治疗的心力衰竭急性加重期似乎也有效。短期内，托伐普坦似乎能缓解急性充血症状并改善死亡率。然而，其对死亡率的长期影响仍存在争议。短期的有利作用归因于选择性V(2)受体阻断，而V(1A)受体未受抑制的刺激可能是缺乏长期益处的一个解释。该药物应在医院环境中开始使用，因为建议仔细监测液体平衡。它通过口服给药，有利于在门诊环境中持续用药。此外，托伐普坦可能在常染色体显性多囊肾病（ADPKD）的治疗中发挥作用。其有效性已在动物模型、3期临床试验中得到证实，目前一项开放标签研究正在进行。由于托伐普坦在肝脏中由细胞色素CYP3A4代谢，医生应注意可能的药物相互作用。大型研究结果表明托伐普坦耐受性良好。常见的副作用有口渴、口干和多尿。托伐普坦不仅在等容性和高容性低钠血症的治疗方面，而且在急性失代偿性心力衰竭的治疗以及可能在ADPKD的治疗方面都开启了新的篇章。
