Nishi Y
Novartis Pharma K.K., 4-17-30 Nishiazabu, Minatoku, Tokyo 106-8618, Japan.
Nihon Yakurigaku Zasshi. 2001 Aug;118(2):107-15. doi: 10.1254/fpj.118.107.
Sandimmun displays considerable inter- and intra-patient variability because its absorption is bile-dependent and affected by concomitant intake of food. Neoral is a microemulsion preconcentrate; a microemulsion is a mixture of the lipophilic active substance with accurately balanced amounts of lipophilic solvent, hydrophilic solvent and surfactant. As the result of advanced microemulsion technique, Neoral has more consistent and improved absorption characteristics. Cyclosporin (cyclosporin A) has been used as an immunosuppressive agent. The major pharmacodynamic action of cyclosporin within T cells is calcineurin inhibition. The complex cyclophilin-cyclosporin competitively binds to the Ca(2+)- and calmodulin-dependent phosphatase calcineurin which then inhibits downstream dephosphorylation and activation of NFAT(transcription factor). The greatest calcineurin inhibition is seen 1-2 h after administration of Neoral in parallel to the highest blood concentration. Variability in cyclosporin exposure was also identified as a risk factor for acute rejection in organ transplant recipients. "Absorption profiling" provides a more accurate prediction of drug exposure and leads to less acute rejection and toxicity. The evolution of Neoral monitoring strategies from trough level to absorption profile will raise the standard of performance of Neoral, resulting in clinical benefits for transplant patients.
山地明显示出患者间和患者内的显著差异，因为其吸收依赖胆汁且受食物同时摄入的影响。新山地明是一种微乳预浓缩液；微乳是亲脂性活性物质与精确平衡量的亲脂性溶剂、亲水性溶剂和表面活性剂的混合物。由于先进的微乳技术，新山地明具有更一致且改善的吸收特性。环孢素（环孢素A）已被用作免疫抑制剂。环孢素在T细胞内的主要药效学作用是抑制钙调神经磷酸酶。亲环蛋白 - 环孢素复合物竞争性结合钙（2 +）和钙调蛋白依赖性磷酸酶钙调神经磷酸酶，进而抑制下游NFAT（转录因子）的去磷酸化和激活。在服用新山地明后1 - 2小时，随着血药浓度达到最高，可见最大程度的钙调神经磷酸酶抑制。环孢素暴露的变异性也被确定为器官移植受者急性排斥反应的一个危险因素。“吸收谱分析”能更准确地预测药物暴露，并减少急性排斥反应和毒性。新山地明监测策略从谷浓度监测到吸收谱分析的演变将提高新山地明的使用标准，从而为移植患者带来临床益处。
