VPA985 IN HYPONATREMIA DUE TO INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION

血管加压素（AVP）是一种肽类激素， 积极参与调节体液渗透压，血液 体积，血压和细胞增殖，通过刺激 特异性膜结合受体分为V1 a-血管，V2- 肾和V3-垂体亚型具有不同的药理学 和细胞内第二信使。 AVP的分泌是维持细胞增殖的绝对必要条件。 如在糖尿病的人和实验模型中所示的流体稳态 尿崩症利钠剂的有效性已被证明 在与水和盐保持相关的条件下。 但 是疾病（充血性心力衰竭的低钠血症，肝硬化， 肾病综合征，以及不适当分泌综合征， 抗利尿激素，SIADH）由于不适当的释放 加压素，特征在于过量的水潴留。 的试剂 通过产生自由水利尿来增加尿量， 在这些条件下有很大的优势。 本研究旨在评价其有效性、安全性和耐受性 VPA-985单次口服给药在低钠血症患者中的应用 SIADH。 此外，初步的药代动力学和药效学 将评估参数。 这项研究刚刚开始， 招聘4 - 6例确诊为SIADH的患者， 18岁和75岁的受试者将在该研究中心入组。

Vasopressin (AVP), the antidiuretic hormone is a peptide hormone actively involved in the regulation of body fluid osmolality, blood volume, blood pressure, and cell proliferation via the stimulation of specific membrane-bound receptors classified into V1a-vascular, V2- renal, and V3-pituitary subtypes having distinct pharmacological profiles and intracellular second messengers. The secretion of AVP is an absolute requirement for the maintenance of fluid homeostasis as shown in human and experimental models of diabetes insipidus. The usefulness of natriuretic agents has been demonstrated in conditions associated with water and salt retention. However, there are diseases (hyponatremia of congestive heart failure, liver cirrhosis, nephrotic syndrome, and the syndrome of inappropriate secretion of antidiuretic hormone, SIADH) due to the inappropriate release of vasopressin and characterized by an excess retention of water. An agent that increases urine output by producing a free water diuresis would be of significant advantage in these conditions. This study is designed to evaluate the efficacy, safety, and tolerance of a single oral dose of VPA-985 in patients with hyponatremia due to SIADH. In addition, preliminary pharmacokinetic and pharmacodynamic parameters will be assessed. This study has just begun patient recruitment. Four to six patients with diagnosed SIADH between the ages of 18 and 75 years will be enrolled at this site.