Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
Drug Research Unit Ghent, Ghent University Hospital, Ghent, Belgium.
Clin Pharmacol Ther. 2019 Jul;106(1):195-203. doi: 10.1002/cpt.1353. Epub 2019 Mar 2.
Generic substitution of antiepileptic drugs is generally not advised by neurologists. The present study investigated the switchability of gabapentin 800 mg tablets (Neurontin and Gabasandoz) using an individual bioequivalence (IBE) study design with two batches of each product and assessed whether between-batch and between-formulation variability in exposure play a significant role in the within-subject variability. The trial was analyzed according to the US Food and Drug Administration (FDA) framework to establish IBE. The IBE was shown between both products with the 95% upper confidence bound of the IBE criterion being -2.01 and -2.31 for area under the concentration-time curve from zero to infinity (AUC ) and peak plasma concentration (C ), respectively. Subject-by-formulation variability (1.35%) was negligible compared with the within-subject variability of AUC with Neurontin (19.0%) and Gabasandoz (23.6%). Inclusion of an additional batch did not significantly change this within-subject variability (20.2% and 23.6%, respectively). This study shows that substitution of gabapentin 800 mg tablets of Neurontin and Gabasandoz should be possible without affecting clinical outcomes.
神经科医生通常不建议将抗癫痫药物进行通用替换。本研究采用个体生物等效性（IBE）设计，对 800mg 剂量的加巴喷丁片（Neurontin 和 Gabasandoz）进行了可替换性研究，评估了暴露的批间和制剂间变异性是否在个体内变异性中起重要作用。该试验根据美国食品和药物管理局（FDA）的框架进行分析，以确定 IBE。结果显示，两种产品之间具有 IBE，IBE 标准的 95%置信上限（C）分别为 AUC 和峰血浆浓度（C）的-2.01 和-2.31。与 Neurontin（19.0%）和 Gabasandoz（23.6%）的 AUC 个体内变异性相比，制剂间变异性（1.35%）可忽略不计。包含额外批次不会显著改变 AUC 的个体内变异性（分别为 20.2%和 23.6%）。本研究表明，替代 Neurontin 和 Gabasandoz 的 800mg 剂量的加巴喷丁片应该是可行的，而不会影响临床结果。
