Cancer Center Amsterdam, Department of Clinical Pharmacology and Pharmacy, VU University Medical Center, Amsterdam, The Netherlands.
Amsterdam Public Health research institute, VU University Medical Center, Amsterdam, The Netherlands.
J Pharm Pharmacol. 2017 Oct;69(10):1265-1274. doi: 10.1111/jphp.12757. Epub 2017 Jun 23.
To compare nilotinib concentrations obtained by venous blood sampling and dried blood spot (DBS) in patients with chronic myeloid leukaemia (CML). It was investigated how to predict nilotinib plasma levels on the basis of DBS.
Forty duplicate DBS and venous blood samples were collected from 20 patients. Capillary blood was obtained by finger prick and spotted on DMPK-C Whatman sampling paper, simultaneously with venous blood sampling. Plasma concentrations were predicted from DBS concentrations using three methods: (1) individual and (2) mean haematocrit correction and (3) the bias between plasma and DBS concentrations. Results were compared using Deming regression and Bland-Altman analysis.
Nilotinib plasma concentrations ranged from 376 to 2663 μg/l. DBS concentrations ranged from 144 to 1518 μg/l. The slope was 0.56 (95% CI, 0.51 to 0.61) with an intercept of -41.68 μg/l (95% CI, -93.78 to 10.42). Mean differences between calculated and measured plasma concentrations were -14.3% (method 1), -14.0% (method 2) and -0.6% (method 3); differences were within 20% of the mean in 73%, 85% and 80% of the samples, respectively. The slopes were respectively 0.96 (95% CI, 0.86 to 1.06), 0.95 (95% CI, 0.86 to 1.03) and 1.00 (95% CI, 0.91 to 1.09).
Plasma concentrations of nilotinib could be predicted on the basis of DBS. DBS sampling to assess nilotinib concentrations in CML patients seems a suitable alternative for venous sampling.
比较慢性髓性白血病（CML）患者静脉血样和干血斑（DBS）中尼洛替尼的浓度。研究了如何基于 DBS 预测尼洛替尼的血浆水平。
从 20 名患者中采集了 40 对重复的 DBS 和静脉血样。通过指尖采血，将血液滴在 DMPK-C Whatman 采样纸上，同时进行静脉血样采集。使用三种方法从 DBS 浓度预测血浆浓度：（1）个体和（2）平均红细胞压积校正和（3）血浆与 DBS 浓度之间的偏差。使用 Deming 回归和 Bland-Altman 分析比较结果。
尼洛替尼的血浆浓度范围为 376 至 2663μg/l。DBS 浓度范围为 144 至 1518μg/l。斜率为 0.56（95%置信区间，0.51 至 0.61），截距为-41.68μg/l（95%置信区间，-93.78 至 10.42）。计算的和测量的血浆浓度之间的平均差异分别为-14.3%（方法 1）、-14.0%（方法 2）和-0.6%（方法 3）；在分别有 73%、85%和 80%的样本中，差异在平均值的 20%以内。斜率分别为 0.96（95%置信区间，0.86 至 1.06）、0.95（95%置信区间，0.86 至 1.03）和 1.00（95%置信区间，0.91 至 1.09）。
可以基于 DBS 预测尼洛替尼的血浆浓度。DBS 采样似乎是评估 CML 患者尼洛替尼浓度的一种合适的替代静脉采样方法。
