Hibberd Adrian D, Trevillian Paul R, Roger Simon D, Wlodarczyk John H, Stein Ann M, Bohringer Elizabeth G, Milson-Hawke Sally M
Newcastle Transplant Unit, Division of Surgery, John Hunter Hospital, Newcastle, New South Wales, Australia.
Transplantation. 2006 Mar 15;81(5):711-7. doi: 10.1097/01.tp.0000181198.98232.0c.
The aim of this study was to determine the bioequivalence of Cysporin, a generic cyclosporine A, compared with Neoral in stable renal transplant recipients.
Study design consisted of an open label, two-way crossover, randomized controlled trial of Cysporin versus Neoral in stable renal transplant recipients. In all, 33 patients were enrolled; 31 were randomized and 28 were evaluable. AUCs(0-12) were done on day 14 and 28; C(0) and C(2) were done on days 0, 7, 21 and 35. Dose conversion was 1:1. Outcome measures for serum cyclosporin A concentrations expressed as the mean+/-SD were AUC(0-12) (microg x hr/L), C(max) (microg/L), C(2) (microg/L), T(max) (hr) and T(1/2) (hr). Mean and 90% CI of the ratio Cysporin/Neoral of log-transformed data were calculated using a general linear model.
The main pharmacokinetic features were: AUC(0-12): Cysporin 3495+/-1319, Neoral 3853+/-1378 (P<0.05); C(max): Cysporin 755+/-301, Neoral 881+/-368 (P<0.05); C(2): Cysporin 613+/-235, Neoral 672+/-255 (P>0.05); T(max): Cysporin 1.9+/-0.8, Neoral 1.4+/-0.6 (P<0.005); and T1/2: Cysporin 8.8+/-4.3, Neoral 8.7+/-6.2 (P>0.05). Estimated ratios of Cysporin/Neoral were: AUC 0.93 (90% CI 0.88-0.98; P<0.05); C(max) 0.88 (90% CI 0.80-0.97; P<0.05); and T(max) 1.32 (90% CI 1.14-1.53; P<0.005).
Both the extent and rate of absorption of Cysporin are significantly less than those of Neoral. The 90% CI for the ratios of Cysporin/Neoral for AUC and C(max) lie within 0.80-1.25. Hence in this clinical context Cysporin is pharmacologically bioequivalent with Neoral. This study illustrates the importance of testing bioequivalence of generic cyclosporine A products in transplant recipients not healthy volunteers.
本研究旨在确定一种环孢素A仿制药Cysporin与新山地明（Neoral）在稳定的肾移植受者中的生物等效性。
研究设计为一项开放标签、双向交叉、随机对照试验，比较Cysporin与Neoral在稳定的肾移植受者中的效果。总共招募了33名患者；31名被随机分组，28名可进行评估。在第14天和第28天测定AUC(0 - 12)；在第0、7、21和35天测定C(0)和C(2)。剂量转换为1:1。血清环孢素A浓度的结果测量值以平均值±标准差表示，包括AUC(0 - 12)（微克×小时/升）、C(max)（微克/升）、C(2)（微克/升）、T(max)（小时）和T(1/2)（小时）。使用一般线性模型计算对数转换数据的Cysporin/Neoral比值的平均值和90%置信区间。
主要药代动力学特征如下：AUC(0 - 12)：Cysporin为3495±1319，Neoral为3853±1378（P<0.05）；C(max)：Cysporin为755±301，Neoral为881±368（P<0.05）；C(2)：Cysporin为613±235，Neoral为672±255（P>0.05）；T(max)：Cysporin为1.9±0.8，Neoral为1.4±0.6（P<0.005）；T1/2：Cysporin为8.8±4.3，Neoral为8.7±6.2（P>0.05）。Cysporin/Neoral的估计比值为：AUC 0.93（90%置信区间0.88 - 0.98；P<0.05）；C(max) 0.88（90%置信区间0.80 - 0.97；P<0.05）；T(max) 1.32（90%置信区间1.14 - 1.53；P<0.005）。
Cysporin的吸收程度和速率均显著低于Neoral。Cysporin/Neoral的AUC和C(max)比值的90%置信区间在0.80 - 1.25内。因此，在这种临床情况下，Cysporin在药理学上与Neoral生物等效。本研究说明了在移植受者而非健康志愿者中测试环孢素A仿制药生物等效性的重要性。
