Milanés C L, Arminio A, Barrios Y, García-Ramírez R, Herrera J, León I, Salgado O, Terán M, Zschaeck D, Weisinger J
Servicio de Nefrología y Trasplante Renal del Hospital Universitario de Caracas.
Invest Clin. 1995 Dec;36(4):183-96.
In an open clinical trial we assessed the tolerance and safety of the 1:1 conversion of traditional cyclosporine A (CyA) to a new cyclosporine formulation based on a microemulsion technology (CyN) in 18 patients with stable renal allografts. 56% patients were female. Median patient age was 40.9 +/- 3.2 years (range 18 to 65). Renal transplantation was performed in 24.1 +/- 4.6 months (range 6 to 67 months), prior to the beginning of the study, and 67% of the transplants were from cadaveric donor. The most frequent underlying renal disease was glomerulonephritis (44.4%). None of the patients entering the study were withdrawn prematurely. After 2 weeks of observation for graft function stability, the study was divided in two phases: I: during 4 weeks the patients received CyA traditional at fixed doses (Mean dose administered 3.056 +/- 0.25 mg/Kg/d) and II: during the consecutive 6 weeks with conversion to CyN, with doses adjustment as required (Mean dose 2.887 +/- 0.21 mg/Kg/d). Clinical events, adverse reactions and laboratory parameters were evaluated. Levels of 100-200 ng/ml measured by monoclonal specific fluorescence polarization immunoassay were considered appropriate. There were no significant changes in physical examination and laboratory parameters between phases. The incidence of adverse reactions reported in phase I was only gingival hypertrophy (5%) which persisted in phase II, qualified as probably related to the cyclosporine, and in phase II tremor in 17%, qualified as definitively related. Both drugs were well tolerated and there was no report of acute rejection during the study. We conclude that the tolerance and safety of the 1:1 conversion of CyA to CyN were confirmed by our results, and considering the improved pharmacokinetic properties of the second, the microemulsion presentation will be used preferentially as immunosuppressive drug in the treatment of stable kidney transplant patients.
在一项开放性临床试验中，我们评估了18例肾移植稳定患者将传统环孢素A（CyA）以1:1比例转换为基于微乳技术的新型环孢素制剂（CyN）后的耐受性和安全性。患者中56%为女性。患者中位年龄为40.9±3.2岁（范围18至65岁）。肾移植在研究开始前24.1±4.6个月（范围6至67个月）进行，67%的移植来自尸体供体。最常见的潜在肾脏疾病是肾小球肾炎（44.4%）。进入研究的患者均未提前退出。在观察移植肾功能稳定性2周后，研究分为两个阶段：第一阶段：在4周内患者接受固定剂量的传统CyA（平均给药剂量3.056±0.25mg/Kg/d）；第二阶段：在接下来的6周内转换为CyN，并根据需要调整剂量（平均剂量2.887±0.21mg/Kg/d）。评估了临床事件、不良反应和实验室参数。通过单克隆特异性荧光偏振免疫测定法测得的100 - 200ng/ml水平被认为是合适的。两阶段之间的体格检查和实验室参数无显著变化。第一阶段报告的不良反应发生率仅为牙龈增生（5%），在第二阶段持续存在，判定可能与环孢素有关，第二阶段震颤发生率为17%，判定肯定与环孢素有关。两种药物耐受性均良好，研究期间未报告急性排斥反应。我们的结果证实了CyA以1:1比例转换为CyN的耐受性和安全性，考虑到第二种药物改善的药代动力学特性，微乳制剂将优先用作稳定肾移植患者的免疫抑制药物。
