PHARMACOKIN&PHARMACODYN INTERACTION OF CORTICOSTEROIDS W/CYCLOSPORINE IN VLNTRS

医药金

• 批准号: 7377815
• 负责人: UWE CHRISTIANS
• 金额: $ 1.83万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377815
• 关键词: PHARMACOKIN&PHARMACODYN; INTERACTION; CORTICOSTEROIDS; CYCLOSPORINE; VLNTRS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cyclosporine and corticosteroids are frequently used drugs in transplant patients to prevent organ rejection. They are associated with a variety of adverse effects, which can shorten the live span of transplant organs and increase the cardiovascular risk of transplant patients. This can lead to premature loss of the transplanted organ or contribute to premature death of transplant patients. When given together both drugs can potentiate each other's negative effects. Although both drugs have been used for more than two decades, surprisingly the exact way in which they interact has never been systematically studied. We have designed a study to investigate the interaction of these two drugs in detail. We want to uncover the basic mechanisms that lead to their toxicity. Since the matter is too complex to be studied in real patients, we propose as a first step a study in healthy volunteers. Study participants will receive low doses of corticosteroids either alone or in combination with cyclosporine. Blood and urine will be collected at defined time points. The samples will then be analyzed in the laboratory to measure drug concentrations. Using complicated laboratory techniques we will also try to identify substances that could be used in the future as markers of drug toxicity. This could help to improve tolerability and safety of immunosuppressive drug therapy in the future.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。环孢素和皮质类固醇是移植患者经常使用的药物，用于预防器官排斥。它们与多种不良反应相关，可缩短移植器官的寿命并增加移植患者的心血管风险。这可能导致移植器官过早丧失或导致移植患者过早死亡。当两种药物一起服用时，会加剧彼此的负面影响。尽管这两种药物已经使用了二十多年，但令人惊讶的是，它们相互作用的确切方式从未被系统研究过。我们设计了一项研究来详细调查这两种药物的相互作用。我们想要揭示导致其毒性的基本机制。由于这个问题太复杂，无法在真实患者中进行研究，因此我们建议第一步对健康志愿者进行研究。研究参与者将单独接受低剂量的皮质类固醇或与环孢菌素联合使用。将在规定的时间点收集血液和尿液。然后将在实验室分析样品以测量药物浓度。我们还将利用复杂的实验室技术尝试识别未来可用作药物毒性标记的物质。这可能有助于提高未来免疫抑制药物治疗的耐受性和安全性。