Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Korea.
Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
J Clin Pharm Ther. 2020 Oct;45(5):1006-1013. doi: 10.1111/jcpt.13124. Epub 2020 Feb 5.
Dried blood spot (DBS) sampling is a minimally invasive method of blood sampling that enables monitoring of drug concentrations to be more convenient. This study aimed at developing a DBS sampling method for an accurate and precise prediction of radotinib plasma concentrations (C ) in patients with chronic myeloid leukaemia (CML).
Dried blood spot and venous blood samples were simultaneously collected from fifty CML patients who had been receiving radotinib for at least a week. Radotinib concentrations were measured using a high-performance liquid chromatographic method with tandem mass spectrometric detection. Unmeasured C was predicted directly based on a Deming regression between DBS concentrations (C ) and C . Unmeasured C was also predicted from C corrected by each patient's haematocrit (Hct). Both prediction methods were evaluated for their accuracy and precision using Deming regression and Bland-Altman analysis.
The Deming regression equation between C and C was obtained as follows: C = 1.34∙C + 4.26 (r = .97). C was directly predictable using C = 1.34∙C + 4.26. With Hct correction, C was alternatively predictable using C = C / (1-Hct + Hct ). The slopes of Deming regression line between predicted and measured C were 0.99 and 1.02 for the direct and Hct-corrected method, respectively. The mean biases (accuracy) were -0.44% and 1.6% with the 95% limits of agreement (precision) of -22.4% to 21.5% and -20.5% to 23.7%, respectively. More than 93% of predicted and measured C pairs had their differences within 20% of the mean of each pair in both methods.
Radotinib C are highly correlated with radotinib C Radotinib C can be accurately and precisely predicted from C using direct or Hct-corrected prediction methods. Both appear to be appropriate for the therapeutic monitoring of radotinib in patients with CML.
干血斑（DBS）采样是一种微创的采血方法，可使药物浓度监测更加方便。本研究旨在建立一种 DBS 采样方法，以准确、精密地预测接受达沙替尼治疗的慢性髓性白血病（CML）患者的达沙替尼血浆浓度（C）。
采集 50 例接受达沙替尼治疗至少 1 周的 CML 患者的 DBS 和静脉血样本。采用高效液相色谱-串联质谱法测定达沙替尼浓度。直接基于 DBS 浓度（C）与 C 的 Deming 回归方程预测未测量的 C。根据每位患者的红细胞压积（Hct）校正 C，也可以预测未测量的 C。使用 Deming 回归和 Bland-Altman 分析评估这两种预测方法的准确性和精密度。
C 与 C 之间的 Deming 回归方程如下：C=1.34×C+4.26（r=.97）。可以直接预测 C=1.34×C+4.26。使用 Hct 校正后，也可以使用 C=C/（1-Hct+Hct）来预测 C。直接和 Hct 校正法的 Deming 回归线斜率分别为 0.99 和 1.02。两种方法的平均偏差（准确性）分别为-0.44%和 1.6%，95%一致性界限（精密度）分别为-22.4%至 21.5%和-20.5%至 23.7%。两种方法中，超过 93%的预测和实测 C 对差值在每个对均值的 20%以内。
达沙替尼 C与达沙替尼 C 高度相关。可通过直接或 Hct 校正预测方法从 C 准确、精密地预测达沙替尼 C。两种方法均适用于 CML 患者达沙替尼的治疗监测。
