VPA985 IN HYPONATREMIA DUE TO INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION

血管加压素(AVP)是一种抗利尿激素，通过刺激V1a-血管、V2-肾和V3-垂体膜受体参与调节体液渗透压、血容量、血压和细胞增殖，具有不同的药理特征和细胞内第二信使。AVP的分泌是维持体液平衡的绝对要求，正如人类和尿崩症的实验模型所显示的那样。利钠药在与水和盐保留有关的条件下已被证明是有用的。然而，也有一些疾病(充血性心力衰竭的低钠血症、肝硬变、肾病综合征和抗利尿激素分泌不当综合征，SIADH)是由于加压素释放不当而导致的，其特征是水分过度滞留。在这种情况下，一种通过产生游离水利尿来增加尿量的试剂将具有显著的优势。本研究旨在评价单剂量口服VPA-985治疗SIADH所致低钠血症的疗效、安全性和耐受性。此外，还将评估初步的药代动力学和药效学参数。这项研究刚刚开始招募病人。本网站将登记4至6名年龄在18岁至75岁之间的被诊断为SIADH的患者。招聘一直很困难。

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. Recruitment has been difficult.