Racial comparisons of everolimus pharmacokinetics and pharmacodynamics in adult kidney transplant recipients.
Racial comparisons of everolimus pharmacokinetics and pharmacodynamics in adult kidney transplant recipients.
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DOI：
10.1097/ftd.0b013e31829a7a7c
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发表时间：
2013-12
影响因子：
2.5
通讯作者：
Baliga P
中科院分区：
文献类型：
--
作者：
Taber DJ;Belk L;Meadows H;Pilch N;Fleming J;Srinivas T;McGillicuddy J;Bratton C;Chavin K;Baliga P
分析依维莫司（EVR）在非洲裔美国人（AA）和高加索人（C）之间的药代动力学（PK）和药效学（PD）特性的数据有限。本研究的目的是确定和比较AA和C成人肾移植受者的EVR PK和浓度相关的疗效和毒性。这是对2006年至2012年期间在南卡罗来纳州医科大学移植中心接受EVR的所有患者进行的回顾性PK和PD分析。43例患者接受了EVR（22例AA，21例C）。基线人口统计学、免疫抑制和免疫风险在种族之间相似，除了既存高血压、死亡供体类型和冷缺血时间在AA患者中更高。PK分析显示，AA患者接受了较高的初始EVR剂量（2.1±0.8 vs 1.6±0.6 mg/天，p=0.036），导致早期EVR浓度较高（前60天EVR > 6 ng/mL：36% vs 10%，p=0.037）。有效性分析表明，EVR对急性排斥反应率（9% vs. 10%，p=0.961）、慢性同种异体移植物变化（18% vs. 14%，p=0.729）和肾功能的影响相似，两组EVR治疗均改善了肌酐清除率（ΔeGFR：27 vs. 12 mL/min/1.73 m2）。毒性分析表明，AA患者的EVR停药率有较高的趋势（46% vs. 19%，p=0.065），腹泻/GI不耐受率显著较高（73% vs. 38%，p=0.022）。这些结果表明，EVR治疗在AA和C型成人肾移植患者中均能有效预防排斥反应并改善移植物功能。与之前在AA患者中进行的哺乳动物雷帕霉素靶蛋白（mTOR）PK/PD分析一致，该研究队列显示AA患者中早期EVR水平较高。
There is limited data analyzing the pharmacokinetic (PK) and pharmacodynamic (PD) properties of everolimus (EVR) between African-Americans (AA) and Caucasians (C). The purpose of this study was to determine and compare the EVR PKs and concentration associated efficacy and toxicity in AA and C adult kidney transplant recipients. This was a retrospective PK and PD analysis of all patients that received EVR at the Medical University of South Carolina Transplant Center between 2006 and 2012. Forty-three patients received EVR (22 AA, 21 C). Baseline demographics, immunosuppression and immunologic risk were similar between races, except for pre-existing hypertension, deceased donor type, and cold ischemic time, which were higher in AA patients. PK analysis revealed AA patients received higher initial EVR doses (2.1±0.8 vs. 1.6±0.6 mg/day, p=0.036), leading to higher early EVR concentrations (EVR >6ng/mL during the 1st 60 days: 36% vs. 10%, p=0.037). Efficacy analysis demonstrated similar EVR effects on acute rejection rates (9% vs. 10%, p=0.961), chronic allograft changes (18% vs. 14%, p=0.729), and renal function, with both groups having improved creatinine clearance with EVR therapy (ΔeGFR: 27 vs. 12 mL/min/1.73 m2). Toxicity analysis demonstrated that AA patients had a trend towards higher rates of EVR discontinuation (46% vs. 19%, p=0.065) and significantly more diarrhea/GI intolerance (73% vs. 38%, p=0.022). These results demonstrate EVR therapy is effective at preventing rejection and improving graft function in both AA and C adult renal transplant patients. Conflicting with previous mammalian Target of Rapamycin (mTOR) PK/PD analyses in AA patients, this study cohort demonstrated higher early EVR levels in the AA patients.