Frei U A, Neumayer H H, Buchholz B, Niese D, Mueller E A
Medizinische Klinik, Nephrologie und Intern, Intensivmedizin, Virchow-Klinikum, Medizinische Fakultät, Humboldt-Universität zu Berlin, Germany.
Transplantation. 1998 Jun 15;65(11):1455-60. doi: 10.1097/00007890-199806150-00008.
A microemulsion formulation of cyclosporine, Neoral, has been developed to overcome the problems associated with the poor and variable absorption of the traditional oil-based oral formulation, Sandimmune. The present study was conducted to compare the safety and tolerability of Neoral versus Sandimmune in maintenance renal transplant recipients over 1 year, and to assess the number of dose adjustments necessary to maintain trough cyclosporine concentrations within the desired therapeutic range. METHODS. Patients on Sandimmune were randomized to be converted to Neoral (n=373) or remain on Sandimmune (n=93) for 12 months.
The proportion of patients needing dose increases to maintain cyclosporine trough levels within the desired range was significantly higher in the Sandimmune group during the first 3 months of the study, whereas the number of patients needing dose reductions was similar in both groups throughout the study period. There were no differences between the groups in terms of changes in blood pressure, serum creatinine levels, or other laboratory parameters. No significant differences in the incidence of adverse events known to be related to cyclosporine were observed between the treatment groups. More adverse events were causally related to Neoral than to Sandimmune by the investigators. However, overall, there were no clinically relevant differences between the treatment groups in the main safety and tolerability variables.
The results of this study in maintenance renal transplant patients suggest that the improved pharmacokinetic characteristics of the microemulsion formulation of cyclosporine, Neoral, may facilitate the clinical management of cyclosporine immunosuppression, compared with the traditional formulation, Sandimmune. Furthermore, there is no evidence that the average improved bioavailability of Neoral has a negative impact on the main safety and tolerability variables, as no significant differences in graft function, the incidence of rejections, and most adverse events were seen.
环孢素的微乳剂制剂新山地明（Neoral）已被开发出来，以克服传统油基口服制剂山地明（Sandimmune）吸收差且吸收不稳定所带来的问题。本研究旨在比较新山地明与山地明在维持性肾移植受者中超过1年的安全性和耐受性，并评估将环孢素谷浓度维持在所需治疗范围内所需的剂量调整次数。方法：接受山地明治疗的患者被随机分为转换为新山地明组（n = 373）或继续使用山地明组（n = 93），为期12个月。
在研究的前3个月，山地明组中需要增加剂量以将环孢素谷水平维持在所需范围内的患者比例显著更高，而在整个研究期间，两组中需要减少剂量的患者数量相似。两组在血压、血清肌酐水平或其他实验室参数的变化方面没有差异。在已知与环孢素相关的不良事件发生率方面，治疗组之间未观察到显著差异。研究者认为与新山地明因果相关的不良事件比与山地明的更多。然而，总体而言，在主要安全性和耐受性变量方面，治疗组之间没有临床相关差异。
这项针对维持性肾移植患者的研究结果表明，与传统制剂山地明相比，环孢素微乳剂制剂新山地明改善的药代动力学特性可能有助于环孢素免疫抑制的临床管理。此外，没有证据表明新山地明平均提高的生物利用度对主要安全性和耐受性变量有负面影响，因为在移植肾功能、排斥反应发生率和大多数不良事件方面未观察到显著差异。
