Bins Sander, Eechoute Karel, Kloth Jacqueline S L, de Man Femke M, Oosten Astrid W, de Bruijn Peter, Sleijfer Stefan, Mathijssen Ron H J
Department of Medical Oncology, Erasmus MC Cancer Institute, PO Box 5201, 3008 AE, Rotterdam, The Netherlands.
Clin Pharmacokinet. 2017 Mar;56(3):305-310. doi: 10.1007/s40262-016-0441-0.
For imatinib, a relationship between systemic exposure and clinical outcome has been suggested. Importantly, imatinib concentrations are not stable and decrease over time, for which several mechanisms have been suggested. In this study, we investigated if a decrease in alpha-1 acid glycoprotein (AGP) is the main cause of the lowering in imatinib exposure over time.
We prospectively measured imatinib trough concentration (C ) values in 28 patients with gastrointestinal stromal tumours, at 1, 3 and 12 months after the start of imatinib treatment. At the same time points, AGP levels were measured.
Overall, imatinib C and AGP levels were correlated (r = 0.656; P < 0.001). However, AGP levels did not fluctuate significantly over time, nor did the change in AGP levels correlate with the change in the imatinib C .
We showed that systemic AGP levels are not likely to be a key player in the decrease in systemic imatinib exposure over time. As long as intra-individual changes in imatinib exposure remain unexplained, researchers should standardize the sampling times for imatinib in order to be able to assess the clinical applicability of therapeutic drug monitoring.
对于伊马替尼，已表明全身暴露与临床结局之间存在关联。重要的是，伊马替尼浓度不稳定且会随时间下降，对此已提出多种机制。在本研究中，我们调查了α-1酸性糖蛋白（AGP）的降低是否是伊马替尼暴露随时间降低的主要原因。
我们前瞻性地测量了28例胃肠道间质瘤患者在伊马替尼治疗开始后1、3和12个月时的伊马替尼谷浓度（C）值。在相同时间点测量AGP水平。
总体而言，伊马替尼C值与AGP水平相关（r = 0.656；P < 0.001）。然而，AGP水平随时间没有显著波动，AGP水平的变化也与伊马替尼C值的变化无关。
我们表明全身AGP水平不太可能是伊马替尼全身暴露随时间降低的关键因素。只要伊马替尼暴露的个体内变化仍无法解释，研究人员就应规范伊马替尼的采样时间，以便能够评估治疗药物监测的临床适用性。
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