Institute of Research and Treatment (IRCCS), Institute of Neurological Sciences of Bologna, Bologna, Italy.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Epilepsia. 2018 Jul;59(7):e103-e108. doi: 10.1111/epi.14446. Epub 2018 Jun 13.
We prospectively examined the effect of antiepileptic (AED) cotherapy on steady state plasma concentrations of perampanel (PMP) in epileptic patients. We classified AEDs as strong enzyme inducers (carbamazepine, phenobarbital, phenytoin, oxcarbazepine), not strong enzyme inducers/not inhibitors (levetiracetam, lamotrigine, topiramate, rufinamide, lacosamide, zonisamide, clobazam), and enzyme inhibitors (valproic acid [VPA]). The main outcome was the comparison of PMP plasma concentration to weight-adjusted dose ratio (C/D; [μg/mL]/mg kg d ) among comedication subgroups. From 79 patients (42 females, 37 males) aged (mean ± standard deviation) 33 ± 13 years (range = 12-66 years), 114 plasma samples were collected. Twenty-eight patients (44 samples) were cotreated with enzyme inducers (group A), 21 (27 samples) with not strong enzyme inducers/not inhibitors (group B), 21 (31 samples) with not strong enzyme inducers/not inhibitors + VPA (group C), and 9 (12 samples) with enzyme inducers + VPA (group D). PMP C/D was reduced (-56%, P < .001) in group A (1.79 ± 0.80) versus group B (4.05 ± 2.16) and increased (P < .001) in group C (6.72 ± 4.04) compared with groups A (+275%), B (+66%), and D (2.76 ± 2.00, +143%). Our study documents the unpublished higher PMP C/D in patients cotreated with VPA. These findings have both theoretical relevance, suggesting better characterization of PMP metabolic pathways with ad hoc studies, and clinical usefulness in managing patients on AED polytherapy.
我们前瞻性地研究了抗癫痫药物（AED）合用对癫痫患者稳态血浆中吡仑帕奈（PMP）浓度的影响。我们将 AED 分为强酶诱导剂（卡马西平、苯巴比妥、苯妥英、奥卡西平）、非强酶诱导剂/非抑制剂（左乙拉西坦、拉莫三嗪、托吡酯、鲁非酰胺、拉科酰胺、唑尼沙胺、氯巴占）和酶抑制剂（丙戊酸[VPA]）。主要结局是比较合用药物亚组之间 PMP 血浆浓度与体重校正剂量比（C/D；[μg/mL]/mg kg d）。共纳入 79 例（42 例女性，37 例男性）年龄（均值±标准差）33±13 岁（范围 12-66 岁）的患者，共采集 114 个血浆样本。28 例（44 个样本）患者合用酶诱导剂（A 组），21 例（27 个样本）合用非强酶诱导剂/非抑制剂（B 组），21 例（31 个样本）合用非强酶诱导剂/非抑制剂+VPA（C 组），9 例（12 个样本）合用酶诱导剂+VPA（D 组）。与 B 组（4.05±2.16）和 C 组（+275%，+66%，+143%）相比，A 组（1.79±0.80）PMP C/D 降低（-56%，P<.001），与 D 组（2.76±2.00，+143%）相比，C 组（6.72±4.04）PMP C/D 升高（P<.001）。本研究发现，VPA 合用患者的 PMP C/D 更高，这一结果之前尚未发表。这些发现具有理论意义，提示需要专门的研究更好地阐明 PMP 的代谢途径，对管理 AED 多药治疗患者具有临床意义。
