Brunet M, Pou L, Manzanares C, Palacios G, Corbella J
Toxicology Service, Hospital Clínic, University of Barcelona, Spain.
Ther Drug Monit. 1998 Dec;20(6):676-9. doi: 10.1097/00007691-199812000-00017.
Tacrolimus is a potent immunosuppressive drug successfully used for baseline and rescue immunosuppression in patients after liver and kidney transplantation. Data from several clinical trials have demonstrated the efficacy of tacrolimus in the prevention of allograft rejection, even at lower concentrations in the therapeutic range (5-15 microg/L). In fact, some patients with tacrolimus levels at less than 5 microg/L have excellent hepatic or kidney function. The limit of detection of the IMx Tacrolimus I assay (TAC I; Abbott Laboratories, IL) is only 5 microg/L and that of the lower tacrolimus calibrator is 10 microg/L. The second-generation assay uses the same monoclonal antibody and the same IMx technology but offers improved sensitivity, with a dynamic range from 0 microg/L to 30 microg/L (lower calibrator, 3 microg/L). The aim of this multicenter study was to evaluate the new IMx Tacrolimus II assay (TAC II) by assessing its precision, sensitivity, performance, and correlation degree relative to the IMx TAC I assay. The study was performed at three centers in Spain. The within-run coefficients of variation (CVs) obtained for the new assay, using each of the trilevel controls in replicates of 20 during 3 consecutive days, were 8.06%, 4.38% and 5.09% at 5 microg/L, 11 microg/L, and 22 microg/L, respectively. The corresponding between-run CVs obtained measuring each of the three controls in duplicate on 10 consecutive days were 9.54%, 6.38% and 5.75%. The limit of detection, with 97.5% confidence, was 1.22 microg/L. TAC II results (Y) were compared with those from the original TAC I assay (X) analyzing 293 whole blood samples from liver (n=145) and kidney (n=148) transplant recipients. The correlation study with patient samples (using the Passing-Bablock method) was y=1.056, x + 0.017, r=0.927. No statistically significant differences were observed between assays (TAC I versus TAC II) in the mean values obtained for total patients (9.89+/-5.42 microg/L versus 10.49+/-5.63 microg/L), liver patients (9.16+/-4.79 microg/L versus 10.00+/-5.20 microg/L), and kidney patients (10.62+/-5.87 micro g/L versus 10.98+/-5.99 microg/L). The new IMx TAC II assay demonstrated the same precision and accuracy that characterized the original assay but showed improved sensitivity to the demands of tacrolimus monitoring in the lower therapeutic range of drug concentrations.
他克莫司是一种强效免疫抑制药物，已成功用于肝肾移植患者的基线免疫抑制和挽救性免疫抑制。多项临床试验数据表明，他克莫司在预防同种异体移植排斥反应方面有效，即使在治疗范围内较低浓度（5 - 15微克/升）时也是如此。事实上，一些他克莫司水平低于5微克/升的患者具有良好的肝肾功能。IMx他克莫司I检测法（TAC I；雅培实验室，伊利诺伊州）的检测限仅为5微克/升，较低的他克莫司校准品为10微克/升。第二代检测法使用相同的单克隆抗体和相同的IMx技术，但灵敏度有所提高，动态范围为0微克/升至30微克/升（较低校准品为3微克/升）。这项多中心研究的目的是通过评估新的IMx他克莫司II检测法（TAC II）相对于IMx TAC I检测法的精密度、灵敏度、性能和相关程度来对其进行评价。该研究在西班牙的三个中心进行。使用三个水平的对照品，在连续3天内每天重复20次，新检测法获得的批内变异系数（CVs）在5微克/升、11微克/升和22微克/升时分别为8.06%、4.38%和5.09%。连续10天每天对三个对照品进行双份测量获得的相应批间CVs为9.54%、6.38%和5.75%。检测限在97.5%置信度下为1.22微克/升。分析来自肝移植（n = 145）和肾移植（n = 148）受者的293份全血样本，将TAC II结果（Y）与原始TAC I检测法（X）的结果进行比较。与患者样本的相关性研究（使用Passing - Bablock方法）为y = 1.056x + 0.017，r = 0.927。在总患者（9.89±5.42微克/升对10.49±5.63微克/升）平均值、肝移植患者（9.16±4.79微克/升对10.00±5.20微克/升）平均值和肾移植患者（10.62±5.87微克/升对10.98±5.99微克/升）平均值方面，两种检测法（TAC I对TAC II）之间未观察到统计学上的显著差异。新的IMx TAC II检测法显示出与原始检测法相同的精密度和准确性，但在药物浓度较低的治疗范围内对他克莫司监测需求的灵敏度有所提高。
