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: 6246458
• 负责人: MARC THIBONNIER
• 金额: $ 1.98万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-06 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6246458
• 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. Up to 20 patients with diagnosed SIADH between the ages of 18 and 75 years will be enrolled.

加压素（AVP），抗利尿激素是积极的肽激素 参与体液渗透压，血容量，血液的调节 压力和细胞增殖通过刺激特定膜 - 分类为V1A血管，V2-肾脏和V3-垂体的结合受体 具有独特的药理学特征和细胞内的亚型 使者。 AVP的分泌是维护的绝对要求 如糖尿病的人类和实验模型所示，流体稳态 平原。在 与水和盐保留有关的条件。 但是，有 疾病（充血性心力衰竭的低钠血症，肝肝硬化， 肾病综合征和不适当分泌的综合征 由于不当释放，抗利尿激素，SIADH） 加压素的特征是水的过量保留。 代理 通过产生免费的水利尿，可以增加尿量 在这些条件下的重要优势。 这项研究旨在评估 由于SIADH引起的低钠血症患者的单一口服VPA-985。 此外，初步的药代动力学和药效学参数 将被评估。 这项研究刚刚开始招募患者。 到 20名在18至75岁之间被诊断为SIADH的患者将 被注册。