Optimal Everolimus Concentration Is Associated With Risk Reduction for Acute Rejection in De Novo Renal Transplant Recipients
Optimal Everolimus Concentration Is Associated With Risk Reduction for Acute Rejection in De Novo Renal Transplant Recipients
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DOI：
10.1097/tp.0b013e3181de1d67
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发表时间：
2010-07-15
期刊：
影响因子：
6.2
通讯作者：
Shaw, Leslie M.
中科院分区：
文献类型：
--
作者：
Chan, Laurence;Hartmann, Erica;Shaw, Leslie M.
背景：依维莫司（Evl）联合他克莫司（Tac）用于初次肾移植是安全有效的。Evl浓度是否影响Tac方案的疗效和安全性尚未报道，目的：评价Evl浓度是否影响活检证实的急性排斥反应（BPAR）、肾功能、不良事件（AE）;并评估药代动力学（PK）相互作用。方法：数据来自一项前瞻性、多中心、开放标签、随机、一项在92例肾移植患者中进行的为期6个月的探索性研究，这些患者接受浓度控制的Evl（目标谷浓度≥ 3 ng/mL）加低剂量Tac或Evl加标准剂量Tac初治;两组均接受巴利昔单抗和皮质类固醇。汇总研究组间的数据，以检查Evl谷水平低于3（n= 26）、3至8（n= 62）或高于8 ng/mL（n= 4）的患者的BPAR率。根据Evl和Tac谷水平对各组进行分层，以评价肾小球滤过率和AE。Evl和Tac的PK相互作用进行了评估，在一个子集的14 patients.Results.Evl谷水平大于或等于3 ng/mL与BPAR率显着降低相比，谷水平小于3 ng/mL。低浓度和标准Tac组6个月时的肾小球滤过率相似。在Evl和Tac之间未观察到明显的PK相互作用。AE不常见，似乎与Evl或Tac水平无关。结论：Evl谷水平≥ 3 ng/mL加Tac与BPAR发生率低相关，且对肾功能无不良影响。Evl和Tac之间不存在明显的PK相互作用。
Background.Everolimus (Evl) plus tacrolimus (Tac) in de novo renal transplantation is effective and safe. Whether the concentration of Evl affects efficacy and safety in a Tac-based regimen has not been previously reported.Aim.To evaluate whether the concentration of Evl affects biopsy-proven acute rejection (BPAR), renal function, adverse events (AEs); and to assess for pharmacokinetic (PK) interactions.Methods.Data were from a prospective, multicenter, open-label, randomized, exploratory 6-month study of 92 renal transplant patients treated de novo with concentration-controlled Evl (target trough levels≥ 3 ng/mL) plus low-dose Tac or Evl plus standard-dose Tac; both groups received basiliximab and corticosteroids. Data were pooled across study arms to examine BPAR rates in patients with Evl trough levels less than 3 (n= 26), 3 to 8 (n= 62), or more than 8 ng/mL (n= 4). Groups were stratified by both Evl and Tac trough levels to evaluate glomerular filtration rate and AEs. Evl and Tac PK interactions were evaluated in a subset of 14 patients.Results.Evl trough level of more than or equal to 3 ng/mL was associated with significantly lower rates of BPAR as compared with a trough level of less than 3 ng/mL. Glomerular filtration rate was similar at 6 months for both the low and standard Tac groups. No apparent PK interactions were observed between Evl and Tac. AEs were infrequent and did not seem to be associated with the Evl or Tac level.Conclusions.Evl trough levels≥ 3 ng/mL plus Tac are associated with low rates of BPAR without adversely affecting renal function. No evident PK interaction exists between Evl and Tac.