Abendroth D
Division of Visceral and Transplant Surgery University of Ulm, Ulm, Germany.
Transplant Proc. 2004 Mar;36(2 Suppl):426S-429S. doi: 10.1016/j.transproceed.2003.12.024.
During the past 20 years, cyclosporine (CsA) has become the main part of immunosuppressive protocols. Its impact to improve the quality and quantity of transplantation surgery has been enormous. Immunosuppression in allograft recipients 10 years after renal transplantation CsA continued to demonstrate benefits on graft survival without evidence of long-term morbidity. The pharmacokinetic properties of CsA show wide interpatient variation. After being subject of intense investigation for more than 20 years, it only recently has the full potential of the drug been realized, primarily due to two advances: first, the development of a microemulsified formulation, (Neoral), that improves drug delivery; second, substantial improvements in CsA monitoring. Sparse-sampling algorithms were developed specifically to predict AUCs. We prospectively investigated the practicality, intrapatient variability, and impact on the outcomes of toxicity and rejection episodes using an algorithm. Rejection episodes were diminished by 43.5% in the first 3 months compared to the results in the previous 3 years. Furthermore, the relation of the trough versus C2 concentrations performed at day 3 to 5 and 10 to 12 predicted the probability of an acute rejection episode. Using a truncated AUC to identify patients at risk for rejection episodes early provides optimal and individualized immunosuppression. This pharmacokinetic rationale has now eventuated in an international consensus statement that represents a further step toward optimal immunosuppression.
在过去20年中，环孢素（CsA）已成为免疫抑制方案的主要组成部分。它对提高移植手术的质量和数量产生了巨大影响。肾移植术后10年，同种异体移植受者使用CsA进行免疫抑制，其在移植物存活方面持续显示出益处，且无长期发病迹象。CsA的药代动力学特性在患者间存在很大差异。经过20多年的深入研究，直到最近才充分认识到该药物的全部潜力，这主要得益于两项进展：第一，开发了微乳化制剂（新山地明），改善了药物递送；第二，CsA监测有了实质性改进。专门开发了稀疏采样算法来预测曲线下面积（AUC）。我们使用一种算法前瞻性地研究了其实用性、患者内变异性以及对毒性和排斥反应结局的影响。与前3年的结果相比，前3个月的排斥反应减少了43.5%。此外，在第3至5天和第10至12天测得的谷浓度与C2浓度之间的关系可预测急性排斥反应的可能性。使用截断的AUC早期识别有排斥反应风险的患者可提供最佳的个体化免疫抑制。这种药代动力学原理现已促成一项国际共识声明，这是朝着最佳免疫抑制迈出的又一步。
