Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
Ther Drug Monit. 2010 Aug;32(4):413-9. doi: 10.1097/FTD.0b013e3181e5c656.
There is a need to monitor everolimus blood concentrations in renal transplant recipients as a result of its high pharmacokinetic variability and narrow therapeutic window. However, analytical methods to determine blood concentrations often differ in performance. Therefore, we investigated whether two commonly used therapeutic drug monitoring methods for everolimus were in agreement and to what extent their differences could lead to differences in dosage advice.
Six hundred twelve whole blood samples were obtained from 28 adult renal transplant recipients receiving everolimus and prednisolone therapy. These samples included 286 everolimus trough concentrations. The remaining samples were obtained up to 6 hours post everolimus intake and allowed calculation of 84 AUCs0-12h. All samples were analyzed with fluorescence polarization immunoassay (FPIA) on an Abbott TDxFLx analyzer and liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Everolimus blood concentrations measured with FPIA and LC-MS/MS were not in agreement. Concentrations determined by FPIA were, on average, 23% higher than concentrations quantified by LC-MS/MS. Moreover, concentrations lower than 15 mug/L or AUC0-12h determined with FPIA could be twofold higher than with LC-MS/MS. This variability can lead to clinically relevant differences in dose adjustment of up to 1.25 mg everolimus despite using a correction factor of 23%. Finally, when trough concentrations were measured with FPIA, higher intrapatient variability was observed compared with the use of LC-MS/MS.
LC-MS/MS outperforms FPIA for clinical drug monitoring and intervention of everolimus therapy in adult renal transplant recipients on dual therapy with prednisolone. Specifically, the use of FPIA can lead to clinically relevant differences in everolimus dosage advice and higher intrapatient variability.
由于依维莫司的药代动力学变异性高和治疗窗狭窄，需要监测肾移植受者的依维莫司血药浓度。然而，用于测定血药浓度的分析方法在性能上往往存在差异。因此，我们研究了两种常用于依维莫司的治疗药物监测方法是否一致，以及它们的差异在多大程度上可能导致剂量建议的差异。
从 28 名接受依维莫司和泼尼松龙治疗的成年肾移植受者中获得了 612 份全血样本。这些样本包括 286 份依维莫司谷浓度。其余样本在依维莫司摄入后 6 小时内获得，允许计算 84 个 AUC0-12h。所有样本均使用荧光偏振免疫测定法（FPIA）在 Abbott TDxFLx 分析仪和液相色谱-串联质谱法（LC-MS/MS）上进行分析。
用 FPIA 和 LC-MS/MS 测定的依维莫司血药浓度不一致。FPIA 测定的浓度平均比 LC-MS/MS 定量的浓度高 23%。此外，用 FPIA 测定的浓度低于 15 µg/L 或 AUC0-12h 可高出 LC-MS/MS 两倍。这种变异性可导致剂量调整的临床相关差异高达 1.25 毫克依维莫司，尽管使用了 23%的校正系数。最后，当用 FPIA 测定谷浓度时，与使用 LC-MS/MS 相比，观察到更高的个体内变异性。
LC-MS/MS 在成人肾移植受者接受泼尼松龙双重治疗时，在依维莫司治疗的临床药物监测和干预方面优于 FPIA。具体而言，使用 FPIA 可能导致依维莫司剂量建议的临床相关差异和更高的个体内变异性。
