Westley Ian S, Taylor Paul J, Salm Paul, Morris Raymond G
Department of Cardiology and Clinical Pharmacology, The Queen Elizabeth Hospital, Woodville, South Australia.
Ther Drug Monit. 2007 Oct;29(5):584-91. doi: 10.1097/FTD.0b013e31811f25df.
The immunosuppressant drug tacrolimus has a narrow therapeutic index and is subject to a large variation in individual bioavailability and clearance. With its narrow therapeutic index, therapeutic drug monitoring is standard clinical practice in the management of transplant recipients. In this study, we report the evaluation of the cloned enzyme donor immunoassay (CEDIA) for the determination of whole-blood tacrolimus concentrations compared with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and microparticle enzyme immunoassay (MEIA) using samples obtained from liver (n = 100) and renal (n = 88) transplant recipients. Linear regression analysis showed a relationship of CEDIA = 1.24 HPLC-MS/MS -0.18 (r = 0.81). The mean bias (+/-SEM) for all patients when compared with HPLC-MS/MS was 22.2% (+/-2.1%). The precision of the CEDIA method for all samples showed a root mean square error of 3.1 microg/L. Liver transplant recipient samples showed a mean (+/-SEM) bias compared with HPLC-MS/MS of 12.5% (+/-1.6%). The precision of the CEDIA method for these samples showed a root mean square error of 1.5 microg/L. The data suggest that in the renal transplant group, the CEDIA and MEIA methods have a bias of 33.3% and 20.1%, respectively, compared with HPLC-MS/MS. The CEDIA tacrolimus immunoassay has been shown to be a rapid method for the determination of whole-blood tacrolimus concentrations and may be considered when HPLC-MS/MS is not available. When used in the clinical setting with other parameters, it would be a useful adjunct in the management of liver transplant recipients, but a significant bias in renal transplant patients needs to be further investigated.
免疫抑制剂他克莫司的治疗指数较窄，个体生物利用度和清除率差异较大。鉴于其治疗指数较窄，治疗药物监测是移植受者管理中的标准临床实践。在本研究中，我们报告了使用从肝移植受者（n = 100）和肾移植受者（n = 88）获取的样本，对克隆酶供体免疫分析（CEDIA）测定全血他克莫司浓度的评估，并与高效液相色谱 - 串联质谱法（HPLC-MS/MS）和微粒体酶免疫分析（MEIA）进行比较。线性回归分析显示CEDIA = 1.24×HPLC-MS/MS - 0.18（r = 0.81）。与HPLC-MS/MS相比，所有患者的平均偏差（±SEM）为22.2%（±2.1%）。CEDIA方法对所有样本的精密度显示均方根误差为3.1μg/L。肝移植受者样本与HPLC-MS/MS相比，平均（±SEM）偏差为12.5%（±1.6%）。CEDIA方法对这些样本的精密度显示均方根误差为1.5μg/L。数据表明，在肾移植组中，与HPLC-MS/MS相比，CEDIA和MEIA方法的偏差分别为33.3%和20.1%。已证明CEDIA他克莫司免疫分析是一种测定全血他克莫司浓度的快速方法，在没有HPLC-MS/MS时可予以考虑。当与其他参数一起用于临床时，它将是肝移植受者管理中的有用辅助手段，但肾移植患者中的显著偏差需要进一步研究。
