Transplantation_i1000.ppt

1、ARCHITECT i1000SR高效全面的移植检测平台,*In Development,Company Confidential 2007 Abbott,Keys To Success,ARCHITECT i1000sr = 高效检测 CHEMIFLEX优化的化学发光技术 检测速度: 100测试/小时 样本装载量:65个 试剂装载量:25个 试剂、样本和耗材的随时上载/下载 简便操作 100 test 包装试剂 日常维护10 分钟 最为全面的移植检测菜单,Company Confidential 2007 Abbott,i1000SR移植相关检测项目,11,Company Confident

2、ial 2007 Abbott,试剂冷藏仓,冷藏仓盖,i1000SR* Internal View,RSH,RV 装载区,吸液针,检测路径,条形码读取器,清洗区,传送装置,Transplant Siver Bullets Internal Use Only,5,免疫抑制剂治疗,免疫抑制剂鸡尾酒疗法,类固醇,首要药物,配合治疗药物,Prednisone,Tacrolimus Prograf,Methylprednisolone,Cyclosporine Neoral/Sandimmune,CellCept - MMF,Azathioprine (GSK,Generic),Sirolimus Ra

3、pamune,Sirolimus Rapamune,Transplant Siver Bullets Internal Use Only,6,免疫抑制治疗的平衡问题,免疫抑制治疗过量 心血管疾病 糖尿病 高血压 高血脂 感染 肾中毒 肿瘤 骨代谢疾病 免疫抑制治疗不足 移植器官排异,谁是赢家?,Transplant Siver Bullets Internal Use Only,8,药物浓度监测 (TDM),MacDonald A, Scarola J, Burke JT, Zimmerman JJ. Clin Ther 2000;22(Suppl B):B101-21.,Transplant

4、 Siver Bullets Internal Use Only,9,临床实验室的挑战: 选用实验方法的检测能力,精密度 再现性 功能灵敏度 可定量报出结果的最低值 (10-20% CV) 准确性/特异性 抗体与代谢物质的交叉反应 其他物质的干扰 与其他方法的相关性 基质中的回收率 线性 线性范围越宽，越少由于稀释而引入的误差，重测次数减少. 定标稳定性 定标稳定性越高，确保连续检测的能力. 更好的精密度,Transplant Siver Bullets Internal Use Only,10,DADE Dimension Analysis,Dimension Xpand Plus with

5、 HM Integrated Chemistry System,Source: Dade Behring company website,Transplant Siver Bullets Internal Use Only,11,SYMPHONY Study,Transplant Siver Bullets Internal Use Only,12,研究结论,结论: 免疫移植疗法包括赛尼哌诱导,麦考酚酸酯 , 低浓度的Tacrolimus 以及皮质类固醇，从而能够在治疗效率（对于急性排异的控制）和毒性（保存移植器官的功能及移植器官存活）间达到最佳平衡点,The New England Jour

6、nal of Medicine, 2007, 357:2562-75,Transplant Siver Bullets Internal Use Only,13,Sirolimus-Based Calcineurin Inhibitor-Sparing Immunotherapy, 6-Year ResultsD.J. Conti et al. ATC Abstract #1525,“The immunosuppressive efficacy of Sirolimus (SIRO) has stimulated efforts to limit calcineurin inhibitor (

7、CNI) exposure in SIRO treated patients. We report our 6-year experience, patients enrolled between 5/01 and 8/02, with a CNI-sparing protocol in 50 consecutive primary renal transplant recipientsRecipients were treated with a triple drug regimen consisting of SIRO, tacrolimus and prednisone. SIRO do

8、sing was adjusted to target a trough level of 10 ng/ml. Tacrolimus剂量在最初的三个月中的谷值浓度为 8-12 ng/ml. 90天开始tacrolimus的剂量降低50%，并持续维持谷值浓度为3 ng/ml.”,Transplant Siver Bullets Internal Use Only,14,移植药物浓度监测的未来,用以诱导和维持免疫抑制的新型的主体免疫抑制剂，由于剂量的减少，从而提高患者的生存质量 低剂量治疗需要临床实验室使用低端浓度精密度更好的灵敏试剂进行药物浓度监测，从而可靠检出移植患者体内所存在的低浓度药物水平

9、,Current Trends in Transplantation Webcast presented by P. Wallemacq on 11/6/2007,Transplant Siver Bullets Internal Use Only,15,2007国际治疗药物监测和临床毒理学会 IATDMCT,Transplant Siver Bullets Internal Use Only,16,共识建议：Tacrolimus 药物浓度监测试剂,更低谷值浓度治疗的新趋势 e.g. SYMPHONY study (谷值浓度: 3-7ng/mL) 检测方法 免疫检测仍然占据常规实验室检测的主导

10、地位 低浓度定量检测能力 (ideally 1ng/mL) 对于免疫及液质联用方法的认证,全美20 50% 的检测结果低于5 ng/mL. 显然，低浓度治疗代表着未来的发展趋势,Transplant Siver Bullets Internal Use Only,17,灵敏度比较,Performed in BE (same lab, same lab technician) ARCHITECT 功能灵敏度 Panel of 5 levels (0.25, 0.50, 1.0, 2.0, 3.0 ng/mL), replicates of 10, two consecutive days 功能灵

11、敏度: 0.61 ng/mL Dade 功能灵敏度 由于干扰，无法检测相同水平组 (基质效应?) 使用全血标本 (0.35, 0.75, 1.5, 3.0, 4.0, and 6.0 ng/mL), replicates of 10, two consecutive days 功能灵敏度: 3.12 ng/mL,Transplant Siver Bullets Internal Use Only,18,功能灵敏度: ARCHITECT vs. Dade,ARCHITECT,Dade,Transplant Siver Bullets Internal Use Only,19,3 ng/mL水平统

12、计学分析: 3 ng/mL真的是3 ng/mL吗?,Data derived from P. Wallemacq, 2007 IATDMCT,Transplant Siver Bullets Internal Use Only,20,不准检测结果的影响,Blood levels targeted at 3 ng/mL,ARCHITECT,Dimension,95% CI = 2.71 3.36 ng/mL,Results obtained are close to target,Drug dose not likely to change,If Result = 1.44 ng/mL,If R

13、esult = 4.15 ng/mL,结果低于标准 提升剂量 发生不良副作用 可能不正确的认为药物依从性差,95% CI = 1.44 4.15 ng/mL,结果高于标准 降低剂量 急性排异反应风险升高,Data derived from P. Wallemacq, 2007 IATDMCT,Tx Recipient,Transplant Siver Bullets Internal Use Only,21,Tacrolimus Proficiency Panel 4 ng/mL,% CV 5.8% 19.2% 23.5% 17.4% 20.6%,这份欧洲数据表明ARCHITECT具有最佳的C

14、V值表现，德灵的在低浓度的CV值表现将近是ARCHITECT的4倍,Transplant Siver Bullets Internal Use Only,22,Silver Bullet #1 灵敏度及精密度表现不佳不能满足用户在低浓度检测时对于准确性的要求,对于免疫抑制剂的不断完善改善了患者的持续生存质量 低剂量用药对于实验室报出准确的血药浓度而言是一个挑战 对于Tacrolimus血液浓度监测现在的要求已下降到 2 ng/mL，这就意味着药物浓度检测试剂的功能灵敏度要达到1 ng/mL，以完成精确的监测要求.,Transplant Siver Bullets Internal Use Only,23,ARCHITECT vs. Dade Tacrolimus 检测表现总结,ARCHI