Wang C-H, Chou N-K, Wu F-L L, Ko W-J, Tsao C-I, Chi N-H, Hsu R-B, Wang S-S
Department of Surgery, National Taiwan University Hospital and College of Medicine, No. 7 Chung-shan South Road, Taipei City, Taiwan.
Transplant Proc. 2006 Sep;38(7):2032-4. doi: 10.1016/j.transproceed.2006.06.038.
This study sought to determine the influence of everolimus on cyclosporine Neoral (CsA) pharmacokinetics over the first 6 months after heart transplantation in Chinese recipients.
Six de novo cardiac recipients receiving a CsA-everolimus-based immunosuppressive regimen after rabbit antithymoglobulin sequential immuno-induction were compared with six age-matched recipients receiving a CsA-azathioprine-based regimen. We compared CsA 12-hour area-under-curve (AUC) of the first dose (PK-1) and steady state dose (PK-S) at 1 month after transplantation. The CsA trough concentrations (Cmin) were compared over the first 6 months after transplantation.
There was no significant difference between the two groups in age, gender, and body weight. With respect to dose-normalized CsA AUC(0-infinity) of PK-1 and dose-normalized CsA AUC(0-12) of PK-S, the difference between the everolimus- and the azathioprine-based regimens was not significant. The dose-normalized CsA trough concentrations (Cmin/dose) were significantly lower in the everolimus-based group than in the azathioprine-based group during the first 5 months after heart transplantation, but the difference was not significant at posttransplantation month 6.
When CsA pharmacokinetic profiles were considered, the CsA dose requirement was not lower in Chinese patients receiving everolimus than that in patients receiving azathioprine. The results differed from reports from Western countries.
本研究旨在确定在中国心脏移植受者中，依维莫司对移植后前6个月环孢素新山地明（CsA）药代动力学的影响。
将6例接受兔抗胸腺细胞球蛋白序贯免疫诱导后采用基于CsA-依维莫司的免疫抑制方案的初发心脏受者，与6例接受基于CsA-硫唑嘌呤方案的年龄匹配受者进行比较。我们比较了移植后1个月时首剂（PK-1）和稳态剂量（PK-S）的CsA 12小时曲线下面积（AUC）。比较了移植后前6个月的CsA谷浓度（Cmin）。
两组在年龄、性别和体重方面无显著差异。就PK-1的剂量标准化CsA AUC(0-∞)和PK-S的剂量标准化CsA AUC(0-12)而言，基于依维莫司和基于硫唑嘌呤的方案之间的差异不显著。在心脏移植后的前5个月，基于依维莫司的组中剂量标准化的CsA谷浓度（Cmin/剂量）显著低于基于硫唑嘌呤的组，但在移植后第6个月差异不显著。
考虑CsA药代动力学特征时，接受依维莫司的中国患者对CsA的剂量需求并不低于接受硫唑嘌呤的患者。该结果与西方国家的报道不同。
