Amante A J, Meier-Kriesche H U, Schoenberg L, Kahan B D
Department of Surgery, University of Texas Medical School at Houston 77030, USA.
Transpl Int. 1997;10(3):217-22. doi: 10.1007/s001470050045.
The initial poor absorption of the corn oil-based, gel capsule oral formulation of cyclosporin (CyA) greatly limits its use for inception of immunosuppressive therapy. Insufficient drug concentrations during the early post-transplant period predispose to renal allograft rejection. The present study served to compare the time required to achieve the therapeutic CyA concentrations after de novo administration of the corn oil-based gel capsule (CyA-GC; n = 11) versus the microemulsion (CyA-ME; n = 11) formulation of CyA. During the 1st month after renal transplantation, patients underwent serial pharmacokinetic profiling from which we obtained observed and dose-corrected values of several parameters. Although patients in neither the CyA-GC nor the CyA-ME group adequately absorbed the drug during days 0-2, from day 3 to 4 patients in the CyA-ME group showed significantly greater absorption than those in the CyA-GC group (P = 0.041). Patients in the CyA-ME group reached the 1st month target average concentration (Cav) values (> or = 550 ng/ml) earlier than those in the CyA-GC group and required significantly lower daily CyA doses (P = 0.018). We conclude that therapeutic CyA levels can be achieved more rapidly and with lower doses of the drug after de novo administration of CyA-ME than with CyA-GC.
环孢素（CyA）基于玉米油的凝胶胶囊口服制剂最初吸收较差，这极大地限制了其在免疫抑制治疗起始阶段的应用。移植后早期药物浓度不足易导致肾移植排斥反应。本研究旨在比较初次给予基于玉米油的凝胶胶囊（CyA-GC；n = 11）与环孢素微乳剂（CyA-ME；n = 11）制剂后达到治疗性CyA浓度所需的时间。在肾移植后的第1个月，患者接受了系列药代动力学分析，从中我们获得了几个参数的观察值和剂量校正值。尽管CyA-GC组和CyA-ME组的患者在第0 - 2天均未充分吸收药物，但从第3天到第4天，CyA-ME组患者的吸收明显高于CyA-GC组（P = 0.041）。CyA-ME组患者比CyA-GC组患者更早达到第1个月的目标平均浓度（Cav）值（≥550 ng/ml），且所需的每日CyA剂量明显更低（P = 0.018）。我们得出结论，与CyA-GC相比，初次给予CyA-ME后能更快且以更低剂量达到治疗性CyA水平。
