Abstract

Here, we developed a novel high-performance liquid chromatography (HPLC) method for quantification of perampanel in clinical practice and investigated the relationships between the plasma concentrations of perampanel obtained by this HPLC method and the CYP3A4*1G polymorphism. The developed HPLC method was validated based on US Food and Drug Administration. The developed HPLC method could be performed with a plasma volume of only 200 μL and had a limit of quantification (LOQ) of 2.5 ng/mL. The coefficients of variation (CVs) for intra- and inter-day assays were less than 10.4 and 7.2%, respectively, and the accuracy was <2.4% for both assays. A total of 12 patients who received 2 mg perampanel had C₀ values ranging from 70.5 to 451 ng/mL, and the CV showed a large variation of 51.4%. No correlations were observed between the dose-adjusted C₀ and the CYP3A4*1G polymorphism. This method was superior to previously reported methods in terms of plasma volume and LOQ and was clinically applicable. Perampanel showed high variations in individual plasma concentrations; however, individual differences could not be predicted from analysis of the CYP3A4*1G polymorphism before perampanel administration. Therefore, after beginning perampanel treatment, the dose should be determined based on the observed plasma concentration.

中文翻译：

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在日本患者中使用高效液相色谱法测定血浆紫杉醇的浓度以及CYP3A4 * 1G多态性的影响。

摘要

在这里，我们开发了一种新型的高效液相色谱（HPLC）方法，用于在临床实践中定量检测过苯丙胺，并研究了通过此HPLC方法获得的过苯丙醇的血浆浓度与CYP3A4 * 1G多态性之间的关系。所开发的HPLC方法已根据美国食品和药物管理局（FDA）进行了验证。可以用仅200μL的血浆体积进行开发的HPLC方法，其定量限（LOQ）为2.5 ng / mL。日内和日间测定的变异系数（CV）分别小于10.4和7.2％，两种测定的准确性均<2.4％。总共12例接受2 mg perampanel的患者的C ₀值范围从70.5至451 ng / mL，CV显示51.4％的较大差异。剂量调整后的C ₀与CYP3A4 * 1G多态性之间没有相关性。就血浆量和LOQ而言，该方法优于先前报道的方法，并且在临床上适用。Perampanel在各个血浆浓度中表现出高度差异；然而，在perampanel给药前无法通过CYP3A4 * 1G多态性分析来预测个体差异。因此，在开始进行perampanel治疗后，应根据观察到的血浆浓度确定剂量。