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.

血管加压素（AVP）是一种抗利尿激素， 参与调节体液渗透压、血容量、血液 压力和细胞增殖通过刺激特定的膜- 结合受体分为V1 a-血管、V2-肾和V3-垂体 具有不同药理学特征的亚型和细胞内第二亚型 使者 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在以下方面得到证实： 与水和盐保留相关的条件。 但有 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， 在这些条件下的优势。 本研究旨在评价以下药物的疗效、安全性和耐受性： SIADH引起的低钠血症患者单次口服VPA-985。 此外，初步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。 高达 20名18至75岁的诊断为SIADH的患者将 被录取