PHARMACOKIN&PHARMACODYN INTERACTION OF CORTICOSTEROIDS W/CYCLOSPORINE IN VLNTRS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。环孢素和皮质类固醇是移植患者常用的预防器官排斥的药物。它们与多种不良反应相关，可缩短移植器官的寿命，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。当两种药物同时服用时，会增强彼此的负面影响。尽管这两种药物已经使用了20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地研究过。我们设计了一项研究来详细研究这两种药物的相互作用。我们想要揭示导致它们毒性的基本机制。由于这个问题太复杂，无法在真正的病人身上进行研究，我们建议首先在健康的志愿者身上进行研究。研究参与者将接受低剂量皮质类固醇单独或与环孢素联合使用。血液和尿液将在规定的时间点采集。然后，这些样品将在实验室进行分析，以测量药物浓度。使用复杂的实验室技术，我们还将尝试确定未来可以用作药物毒性标记的物质。这有助于提高免疫抑制药物治疗的耐受性和安全性。

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.