Sharma A, Shekhar C, Heer M, Minz M
Department of Transplant Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Transplant Proc. 2006 Sep;38(7):2051-3. doi: 10.1016/j.transproceed.2006.07.004.
The bioequivalence of generic formulations is established by measuring pharmacokinetic parameters in healthy volunteers. Cyclosporine (CsA) absorption and exposure is known to differ between healthy volunteers and transplant recipients. Therefore bioequivalence testing may be inadequate to ensure therapeutic equivalence. We sought to compare the efficacy of generic cyclosporine (ArpimuneME, RPG Life Sciences) versus Sandimmune Neoral in de novo renal transplant recipients.
A prospective single-center, open-label study enrolled 20 de novo renal transplant patients (group 1: mean age 30.55 +/- 9.81 years, M:F 19:1, mean donor age 43.4 +/- 10.8). All patients received ArpimuneME along with azathioprine and prednisolone. The results were compared with 17 matched controls (group 2: mean age 28.1 +/- 9.5 years, M:F 13:4, mean donor age 47.8 +/- 6.8) who received Neoral and were transplanted during the same period. C(2) levels were monitored by the cloned enzyme donor immunoassay (CEDIA).
Patient and graft survivals were 100% and 100% and 100% and 92.8% in groups 1 and 2, respectively (P = NS). Six patients (30%) experienced rejection in group 1 as compared eight patients (47.1%) in group 2. Mean CsA levels (ng/mL) during the first month were 1419.1 +/- 213.6 and 1460.5 +/- 290.7 and at 3 months, 1296.3 +/- 227.8 and 1342.4 +/- 303.4 in the two groups, respectively (P = NS). The mean serum creatinine levels (mg%) in group 1 and group 2 were 1.6 +/- 0.8 and 2.0 +/- 1.4 at discharge and 1.5 +/- 0.4 and 1.5 +/- 0.8 at 6 months, respectively (P = NS).
Use of a generic microemulsion form of CsA provided safe and effective immunosuppression compared with Sandimmune Neoral when drug monitoring was performed by C(2) levels.
通用制剂的生物等效性是通过在健康志愿者中测量药代动力学参数来确定的。已知环孢素（CsA）在健康志愿者和移植受者中的吸收和暴露情况存在差异。因此，生物等效性测试可能不足以确保治疗等效性。我们试图比较通用型环孢素（ArpimuneME，RPG生命科学公司）与新山地明（Sandimmune Neoral）在初治肾移植受者中的疗效。
一项前瞻性单中心、开放标签研究纳入了20例初治肾移植患者（第1组：平均年龄30.55±9.81岁，男∶女为19∶1，供者平均年龄43.4±10.8岁）。所有患者均接受ArpimuneME联合硫唑嘌呤和泼尼松龙治疗。将结果与17例匹配的对照者（第2组：平均年龄28.1±9.5岁，男∶女为13∶4，供者平均年龄47.8±6.8岁）进行比较，这些对照者接受新山地明治疗且在同一时期接受移植。通过克隆酶供体免疫测定法（CEDIA）监测C（2）水平。
第1组和第2组的患者和移植物存活率分别为100%和100%以及100%和92.8%（P=无显著性差异）。第1组有6例患者（30%）发生排斥反应，而第2组有8例患者（47.1%）发生排斥反应。两组在第1个月时的平均CsA水平（ng/mL）分别为1419.1±213.6和1460.5±290.7，在3个月时分别为1296.3±227.8和1342.4±303.4（P=无显著性差异）。第1组和第2组出院时的平均血清肌酐水平（mg%）分别为1.6±0.8和2.0±1.4，6个月时分别为1.5±0.4和1.5±0.8（P=无显著性差异）。
当通过C（2）水平进行药物监测时，与新山地明相比，使用通用型微乳剂形式的CsA可提供安全有效的免疫抑制作用。
