Therapeutic drug monitoring of free perampanel concentrations in practice: A practical analytical technique based on centrifugal ultrafiltration sample separation

治疗药物游离吡仑帕奈浓度的监测实践:基于离心超滤样品分离的实用分析技术

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作者:Ying-Hua Ma, Lei Dong, Jia-Xuan Wu, Shi-Yuan Hu, Xiang-Fei Meng, Yi-Le Zhao, Kang Liu, Dan-Ni Yan, Su-Zhen Sun

Conclusions

The proposed method is efficient, sensitive, and suitable for detecting free PER concentrations in children with epilepsy. Simultaneously, the free PER concentration response to clinical outcomes in children with epilepsy was more clinically significant, particularly when combined with VPA.

Methods

Free PER concentration was obtained using centrifugal ultrafiltration devices. The internal standard was PER-D5. The method was investigated for selectivity, carryover, lower limit of quantification, calibration curve, accuracy, precision, matrix effects, recovery, and stability. The Spearman's correlation coefficient was used to evaluate the correlation between the free and total PER concentrations. A nonparametric test was used to estimate the effects of PER along with other antiepileptic drugs on the total and free PER concentrations.

Results

The free PER concentration was positively correlated with the total PER concentration in the 57 plasma samples (r = 0.793 > 0, P < 0.001). Additionally, the free PER concentrations were significantly (P < 0.05) increased in valproic acid (VPA) co-therapy (9.87 ± 5.83) compared with non-VPA co-therapy (5.03 ± 4.57). Conclusions: The proposed method is efficient, sensitive, and suitable for detecting free PER concentrations in children with epilepsy. Simultaneously, the free PER concentration response to clinical outcomes in children with epilepsy was more clinically significant, particularly when combined with VPA.

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