Barone G, Chang C T, Choc M G, Klein J B, Marsh C L, Meligeni J A, Min D I, Pescovitz M D, Pollak R, Pruett T L, Stinson J B, Thompson J S, Vasquez E, Waid T, Wombolt D G, Wong R L
Department of Vascular and Transplant Surgery, University of Arkansas, Little Rock 72205-7199, USA.
Transplantation. 1996 Mar 27;61(6):875-80. doi: 10.1097/00007890-199603270-00005.
This study was a randomized, double-blind, 12-week comparison of the pharmacokinetics, safety, and tolerability of two cyclosporine (CsA) formulations, cyclosporine emulsion capsules and oral solution for microemulsion and cyclosporine, in the postoperative management of renal transplant patients. Of the 101 patients, aged 18 to 65, who entered the study, 89 were evaluable for pharmacokinetics. Initial dosage was 10 mg/kg per day, administered twice daily in two equal doses. Dosages were adjusted to achieve target CsA concentrations. The pharmacokinetic (PK) parameters (dose-normalized) of greatest interest were maximum blood concentration (C(max)/dose), time to reach maximum concentration (t(max), area under the blood concentration-vs.-time curve (AUC/dose), and trough blood concentrations (Co h/dose). The relative CsA bioavailabilty was found to be significantly enhanced with cyclosporine emulsion compared with cyclosporine with a 16% to 31% increase in AUC and a 32% to 42% increase in C(max). Intrapatient variability of PK parameters was significantly lower with cyclosporine emulsion than with cyclosporine for AUC, C(oh), t(max), and C(max) in many instances. This indicates a more consistent, rapid, and more complete total absorption of CsA. Despite higher CsA C(max) levels and AUCs with cyclosporine emulsion, safety and tolerability (detailed in a parallel report) were comparable to those of cyclosporine. The PK advantages of cyclosporine emulsion over cyclosporine are either independent of food conditions or possibly reflective of more consistent absorption of CsA with cyclosporine emulsion. The findings suggest that de novo use of cyclosporine emulsion may simplify and improve management of organ transplant recipients and that the PK advantages of cyclosporine emulsion may translate into clinical benefits.
本研究为一项随机、双盲、为期12周的比较研究，对比了两种环孢素（CsA）制剂——环孢素乳剂胶囊与微乳环孢素口服溶液——在肾移植患者术后管理中的药代动力学、安全性和耐受性。在101名年龄在18至65岁之间进入本研究的患者中，89名可进行药代动力学评估。初始剂量为每日10mg/kg，分两次等量给药。调整剂量以达到目标CsA浓度。最受关注的药代动力学（PK）参数（剂量标准化）为最大血药浓度（C(max)/剂量）、达峰时间（t(max)）、血药浓度-时间曲线下面积（AUC/剂量）以及谷血药浓度（Co h/剂量）。与环孢素相比，环孢素乳剂可显著提高CsA的相对生物利用度，AUC增加16%至31%，C(max)增加32%至42%。在许多情况下，环孢素乳剂的PK参数患者内变异性显著低于环孢素，包括AUC、C(oh)、t(max)和C(max)。这表明CsA的总吸收更一致、快速且更完全。尽管环孢素乳剂的CsA C(max)水平和AUC更高，但其安全性和耐受性（在一份平行报告中有详细阐述）与环孢素相当。环孢素乳剂相对于环孢素的PK优势要么与食物条件无关，要么可能反映出环孢素乳剂对CsA的吸收更一致。研究结果表明，新使用环孢素乳剂可能会简化并改善器官移植受者的管理，且环孢素乳剂的PK优势可能转化为临床益处。
