VPA985 IN HYPONATREMIA DUE TO INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION

VPA985 由于抗利尿激素分泌不当而出现低钠血症

• 批准号: 6115286
• 负责人: MARC THIBONNIER
• 金额: $ 1.92万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6115286
• 关键词: body fluid balance therapy; clinical research; drug screening /evaluation; human subject; human therapy evaluation; hyponatremia; oral administration; secretion; vasopressins

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.

加压素（AVP），抗利尿激素是一种肽激素，积极参与体液渗流性，血容量，血压和细胞增殖，通过刺激特定的膜结合受体分类为V1A-血管，V2-肾脏，V3 pitiutiutary subserss的特定膜结合受体，并构成了不同的药物。 AVP的分泌是维持液体稳态的绝对要求，如糖尿病的人类和实验模型所示。 在与盐和盐保留有关的条件下，已经证明了亚钠剂的有用性。 然而，由于不适当释放了加压素，并以水的过多释放而表征，由于不当分泌抗毒素激素的不适当分泌，抗利尿激素的不适当分泌不适当地分泌不适当的疾病（肝硬化，肾病综合征和不适当分泌的综合征）疾病。 在这些条件下，通过产生游离水利尿剂来增加尿液输出的药物将具有重要优势。这项研究旨在评估单个口服剂量VPA-985对由于SIADH引起的低钠血症患者的疗效，安全性和耐受性。 此外，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患者。 该站点将招募四至6名被诊断为18至75岁之间的SIADH患者。 招募很困难。