Wahlberg J, Wilczek H E, Fauchald P, Nordal K P, Heaf J G, Olgaard K, Hansen J M, Lokkegaard H, Mueller E A, Kovarik J M
Department of Transplantation Surgery, University Hospital, Uppsala, Sweden.
Transplantation. 1995 Oct 15;60(7):648-52. doi: 10.1097/00007890-199510150-00005.
To evaluate the pharmacokinetic properties of the new microemulsion formulation of cyclosporine (Sandimmun Neoral), a double-blind, prospective study in stable renal transplant recipients was performed. The patients were randomized on a 4:1 basis either to receive Sandimmun Neoral (n = 45) or continue on regular Sandimmun (n = 12). Before randomization, a steady-state pharmacokinetic profile study was performed in all patients while they were still on regular Sandimmun. Pharmacokinetic assessments were then performed after 8 and 12 weeks and after 1 year. A milligram-to-milligram dose conversion was shown to be adequate to maintain the patients within a predefined target therapeutic window. Changes in pharmacokinetic parameters after conversion to Sandimmun Neoral were consistent with an increased rate and extent of cyclosporine absorption from the Neoral formulation. This was reflected by a shorter time to reach peak concentration and also by a mean increase in peak concentration by 67%, and an overall mean increase in drug exposure (area under the curve) by 34%. These findings were also confirmed 1 year after conversion. Furthermore, significantly reduced intraindividual variability in pharmacokinetic parameters was found, as well as improvements in the correlation between trough concentrations and area under the curve after conversion to Sandimmun Neoral. In conclusion, our results indicate an improved and consistent absorption of cyclosporine from the Neoral formulation, which should make clinical management easier and safer.
为评估环孢素新微乳剂配方（新山地明）的药代动力学特性，对稳定的肾移植受者进行了一项双盲前瞻性研究。患者按4:1的比例随机分组，分别接受新山地明（n = 45）或继续使用常规山地明（n = 12）。在随机分组前，所有患者仍使用常规山地明时进行了稳态药代动力学剖析研究。然后在8周、12周和1年后进行药代动力学评估。结果表明，毫克对毫克的剂量转换足以使患者维持在预定的目标治疗窗内。转换为新山地明后，药代动力学参数的变化与新山地明配方中环孢素吸收速率和程度的增加一致。这表现为达到峰值浓度的时间缩短，峰值浓度平均增加67%，药物暴露（曲线下面积）总体平均增加34%。转换1年后这些发现也得到了证实。此外，还发现药代动力学参数的个体内变异性显著降低，转换为新山地明后谷浓度与曲线下面积之间的相关性也有所改善。总之，我们的结果表明新山地明配方中环孢素的吸收得到改善且一致，这应会使临床管理更轻松、更安全。
