BUCILLAMINE AND RADIOCONTRAST - INDUCED NEPHROPATHY

布西拉明和放射造影 - 诱发肾病

• 批准号: 6993083
• 负责人: LAWRENCE HORWITZ
• 金额: $ 10万
• 依托单位: KEYSTONE BIOMEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-05 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6993083
• 关键词: acute renal failure; antioxidants; bioimaging /biomedical imaging; chemoprevention; contrast media; creatinine; cytokine; diagnosis procedure safety; disease /disorder model; drug adverse effect; drug screening /evaluation; histopathology; iatrogenic disease; immunomodulators; kidney disorder chemotherapy; kidney disorder diagnosis; kidney imaging /visualization; kidney necrosis; kidney pharmacology; laboratory rat; nonhuman therapy evaluation; oxidative stress; oxidoreductase inhibitor; pharmacokinetics; renal ischemia /hypoxia; renal toxin; therapy design /development

DESCRIPTION (provided by applicant): It is proposed to test in animal models the potential efficacy of administration of bucillamine a potent antioxidant and immunomodulating agent for prevention of radiocontrast-induced nephropathy. Both intravenous and oral administration of bucillamine will be investigated in two separate rat models relevant to clinical radiocontrast-induced worsening of renal disease. One is a model of acute tubular necrosis due to transient ischemia by clamping the renal pedicals and the other is a model of radio contrast-induced renal necrosis following pretreatment with a nitric oxide inhibitor. Bucillamine has been effective in reducing cardiac, liver or lung injury due to oxidative or reperfusion stress in animal models. Renal injury due to contrast agents has considerable similarity to these settings in that it also appears to be related to transient ischemia and oxidative stress. Bucillamine has been demonstrated to be safe in normal humans with intravenous administration in Phase I studies and has been a successful oral treatment for rheumatoid arthritis in foreign markets. Keystone Biomedical has patent protection for use of bucillamine in oxidative and reperfusion injury. Use of radiocontrast agents for clinical diagnostic tests in patients with renal abnormalities is frequently necessary but is associated with a risk of worsening the renal impairment. There is an urgent need for a treatment to reduce the risk of worsening renal disease due to radiocontrast exposure. A successful treatment would garner a very large market in the U.S. and abroad. If the proposed studies are successful the applicant will apply for funds for Phase II studies to confirm proof of principle of this treatment in humans and to assess optimal dosing. Subsequently commercial funding for Phase III studies aimed at gaining sufficient verification of efficacy to acquire markeing approval through the Food and Drug Administration will be sought.

描述（由申请人提供）：拟在动物模型中测试buillamine给药的潜在功效，buillamine是一种有效的抗氧化剂和免疫调节剂，用于预防放射性造影剂引起的肾病。静脉注射和口服布吉拉明将在两种不同的大鼠模型中进行研究，这些模型与临床放射造影剂引起的肾脏疾病恶化有关。一种是夹持肾蒂引起的暂时性缺血急性肾小管坏死模型，另一种是用一氧化氮抑制剂预处理后放射性造影剂诱导的肾坏死模型。在动物模型中，buillamine可有效减轻氧化或再灌注应激引起的心脏、肝脏或肺损伤。造影剂引起的肾损伤与这些情况有相当大的相似性，因为它似乎也与短暂缺血和氧化应激有关。buillamine在I期研究中已被证明对正常人体静脉注射是安全的，并且在国外市场已成功用于类风湿性关节炎的口服治疗。Keystone Biomedical在氧化和再灌注损伤中使用buillamine已获得专利保护。