Med. Klinik mS Nephrologie, Universitätsmedizin Charité, Berlin, Germany.
Expert Opin Drug Metab Toxicol. 2011 Jan;7(1):103-13. doi: 10.1517/17425255.2011.540238. Epub 2010 Dec 8.
The prevalence of acute renal allograft rejection has decreased substantially in past decades due to new and more specific immunosuppressive compounds but improvements in long-term graft function have not been achieved. There is a large need for new immunosuppressive agents that lack toxicity of current agents such as calcineurin inhibitors but show high synergistic efficiency in preventing rejection processes.
This review summarizes data concerning the pharmacokinetics, pharmacodynamics and clinical efficacy of the new PKC inhibitor sotrastaurin with a focus on renal transplantation. The article contains information that has been presented at international transplant meetings and congresses and that has been published between 2006 and 2010. Additionally, current ongoing trials are described in detail.
Immunosuppressive regimens after kidney transplantation consist of a combination of several agents in order to minimize drug toxicity. Therefore, the reader is presented with the most up-to-date/current developments in sotrastaurin applications in Phase I and II trials with emphasis on data maintained from studies that combined sotrastaurin with established agents such as mycophenolic acid and tacrolimus.
Several trials are ongoing and planned to determine the optimal immunosuppressive regimen to benefit from sotrastaurin's distinct mechanism of action.
在过去几十年中，由于新的和更具特异性的免疫抑制剂化合物的出现，急性肾移植排斥反应的发生率已经大大降低，但长期移植物功能的改善尚未实现。因此，我们非常需要新的免疫抑制剂，这些抑制剂缺乏当前药物（如钙调神经磷酸酶抑制剂）的毒性，但在预防排斥反应方面具有很高的协同效率。
本综述总结了新型蛋白激酶 C 抑制剂 sotrastaurin 的药代动力学、药效学和临床疗效数据，重点是肾移植。本文包含了在国际移植会议和大会上发表的信息，这些信息发表于 2006 年至 2010 年之间。此外，还详细描述了当前正在进行的试验。
肾移植后免疫抑制方案由几种药物联合组成，以最大程度地降低药物毒性。因此，读者将了解 sotrastaurin 在 I 期和 II 期试验中的最新/当前进展情况，重点是从将 sotrastaurin 与已建立的药物（如霉酚酸和他克莫司）联合使用的研究中获得的数据。
正在进行和计划进行几项试验，以确定最佳免疫抑制方案，从而从 sotrastaurin 的独特作用机制中获益。
