PILOT STUDY OF TUDCA DOSING AND PHARMACOKINETICS IN NONHUMAN PRIMATES

TUDCA 在非人类灵长类动物中的剂量和药代动力学试点研究

• 批准号: 8357872
• 负责人: MARTHA NEURINGER
• 金额: $ 4.36万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357872
• 关键词: Animal Model; Animals; Bile Acids; Clinical Trials Design; Degenerative Disorder; Dose; Drug Kinetics; Funding; Goals; Grant; Human; Macaca mulatta; Metabolism; National Center for Research Resources; Neurodegenerative Disorders; Neuroprotective Agents; Oral; Organ; Patients; Pharmacodynamics; Physiology; Pilot Projects; Plasma; Primates; Principal Investigator; Regimen; Research; Research Infrastructure; Resources; Retinal; Retinal Degeneration; Retinal Diseases; Rodent; Rodent Model; Source; Therapeutic; United States National Institutes of Health; cost; nonhuman primate; tauroursodeoxycholic acid; Animal Model; Animals; Bile Acids; Clinical Trials Design; Degenerative Disorder; Dose; Drug Kinetics; Funding; Goals; Grant; Human; Macaca mulatta; Metabolism; National Center for Research Resources; Neurodegenerative Disorders; Neuroprotective Agents; Oral; Organ; Patients; Pharmacodynamics; Physiology; Pilot Projects; Plasma; Primates; Principal Investigator; Regimen; Research; Research Infrastructure; Resources; Retinal; Retinal Degeneration; Retinal Diseases; Rodent; Rodent Model; Source; Therapeutic; United States National Institutes of Health; cost; nonhuman primate; tauroursodeoxycholic acid

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Tauroursodeoxycholic acid (TUDCA) is a bile acid that has shown promise as a neuroprotective agent in rodent models of retinal degeneration and neurodegenerative disease. However, there are no studies showing target organ benefit with oral dosing. Before full-scale studies are undertaken in human patients with retinal disease, we need to better understand the pharmacokinetics and pharmacodynamics of the orally dosed compound in a relevant animal model. This study has the goal of identifying a potentially therapeutic dose and dosing regimen of TUDCA. Specifically, we propose to determine an oral dose that, at steady state plasma concentration, achieves a retinal level found to be therapeutic in rodent studies, and further, to determine whether vitreous and CSF levels can function as surrogates for retinal levels of TUDCA. The animal of choice is the rhesus macaque because of the similarity in bile acid metabolism and retinal physiology in humans and nonhuman primates. The study will provide key information needed for the design of clinical trials in human patients with retinal degenerative diseases.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 牛ta牛脱氧胆酸（TUDCA）是一种胆汁酸，在视网膜变性和神经退行性疾病的啮齿动物模型中表现出有望为神经保护剂。 但是，尚无研究表明靶心器官的口服给药益处。 在对视网膜疾病的人类患者进行全面研究之前，我们需要更好地了解相关动物模型中口服剂量化合物的药代动力学和药效学。 这项研究的目的是确定TUDCA的潜在治疗剂量和给药方案。 具体而言，我们建议确定一种口服剂量，即在稳态血浆浓度下，在啮齿动物研究中发现具有治疗性的视网膜水平，并进一步确定玻璃体和CSF水平是否可以充当TUDCA视网膜水平的替代物。 选择的动物是恒河猕猴，因为人类和非人类灵长类动物的胆汁酸代谢和视网膜生理学的相似性。 该研究将为视网膜退行性疾病患者设计临床试验设计所需的关键信息。