Regazzi M B, Molinaro M, Tinelli C, D'Eril G M, Goggi C, Campana C, Fiorito V, Moratti R, Viganò M
Department of Pharmacology, IRCCS-Policlinico S. Matteo, University of Pavia, Italy.
Ther Drug Monit. 2000 Dec;22(6):712-5. doi: 10.1097/00007691-200012000-00010.
The authors performed a comparative analysis of 60 whole blood samples containing cyclosporine (CsA) from heart transplant (HTx) recipients (n = 60) by the two "specific" monoclonal immunoassays, enzyme-multiplied immunoassay technique (EMIT) and fluorescence polarization immunoassay (S-FPIA), using the Altman-Bland approach based on graphical techniques and simple calculations. The CsA blood concentrations measured by S-FPIA [mean (SD): 268.1 (108.8) ng/mL] showed a statistically significant difference (P < 0.001) from the corresponding concentrations measured by EMIT [219.6 (118.7) ng/mL]. The CsA concentrations were 27% (median) higher when determined by monoclonal S-FPIA than by EMIT. The comparison between EMIT and S-FPIA showed a good correlation (S-FPIA conc. (ng/mL) = EMIT conc. (ng/mL) x 0.88 + 76.1, r = 0.96, P < 0.001). However, a high correlation does not mean that the two methods agree, and their use as interchangeable might be misleading. The authors summarized the degree of agreement by calculating the bias estimated by the mean difference (d) and the standard deviation of the difference (SD). For CsA concentration data, the mean difference (S-FPIA minus EMIT) is +49.9 ng/mL and SD is 31.2 ng/mL. Altman-Bland analysis indicates considerable lack of agreement between EMIT and S-FPIA, with discrepancies of more than 100 ng/mL. The present study's data clearly show that there is a considerable and clinically unacceptable lack of agreement between the S-FPIA and the EMIT techniques in HTx recipients for the whole range of concentrations evaluated (25-500 ng/mL), and this is caused by the variation in the overestimation of the CsA parent compound. Even though a similar CsA reference range was reported during maintenance therapy for both methods (150-250 ng/mL), which might encourage their interchangeability in the clinical setting, this approach should be avoided. Laboratory reports should always state both the concentration of CsA and the analytical method.
作者采用基于图形技术和简单计算的奥特曼-布兰德方法，通过两种“特异性”单克隆免疫测定法，即酶增强免疫测定技术（EMIT）和荧光偏振免疫测定法（S-FPIA），对60份来自心脏移植（HTx）受者（n = 60）且含有环孢素（CsA）的全血样本进行了比较分析。S-FPIA测定的CsA血药浓度[均值（标准差）：268.1（108.8）ng/mL]与EMIT测定的相应浓度[219.6（118.7）ng/mL]相比，差异具有统计学意义（P < 0.001）。单克隆S-FPIA测定的CsA浓度比EMIT测定的高27%（中位数）。EMIT与S-FPIA之间的比较显示出良好的相关性（S-FPIA浓度（ng/mL）= EMIT浓度（ng/mL）×0.88 + 76.1，r = 0.96，P < 0.001）。然而，高相关性并不意味着两种方法一致，将它们互换使用可能会产生误导。作者通过计算平均差异（d）估计的偏差和差异的标准差（SD）来总结一致程度。对于CsA浓度数据，平均差异（S-FPIA减去EMIT）为+49.9 ng/mL，SD为31.2 ng/mL。奥特曼-布兰德分析表明，EMIT和S-FPIA之间存在相当大的不一致，差异超过100 ng/mL。本研究数据清楚地表明，在HTx受者中，对于评估的整个浓度范围（高达500 ng/mL），S-FPIA和EMIT技术之间存在相当大且临床上不可接受的不一致，这是由CsA母体化合物高估的差异导致的。尽管两种方法在维持治疗期间报告的CsA参考范围相似（150 - 250 ng/mL），这可能会促使它们在临床环境中互换使用，但应避免这种做法。实验室报告应始终注明CsA的浓度和分析方法。
