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: 6276520
• 负责人: MARC THIBONNIER
• 金额: $ 1.83万
• 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: 1997-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6276520
• 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.

加压素(AVP)是一种抗利尿激素，是一种多肽激素。 积极参与体液渗透压、血液的调节 体积、血压和细胞增殖通过刺激 特异性膜结合受体分为V1a-血管、V2- 肾型和V3-垂体亚型具有不同的药理作用 简档和细胞内第二信使。 AVP的分泌是维持血管紧张素转换酶的绝对要求 在人类和糖尿病实验模型中显示的液体稳态 尿崩症。利钠药的用处已得到证实。 在与水和盐保持相关的条件下。然而，在那里 是否有疾病(充血性心力衰竭低钠血症、肝硬变、 肾病综合征，和不适当分泌的综合征 抗利尿激素，SIADH)由于不适当的释放 后叶加压素，特征是水分过度滞留。一名代理 通过产生一种游离的水利尿来增加尿量 在这些条件下具有显著的优势。 本研究旨在评估阿司匹林的有效性、安全性和耐受性。 单剂量口服VPA-985治疗慢性阻塞性肺疾病所致低钠血症 希阿德。此外，初步的药代动力学和药效学 将对参数进行评估。这项研究才刚刚开始，病人 招聘。4至6名确诊为SIADH的患者 18岁和75岁的学生将在该网站注册。