儿童癫痫患者的氨己烯酸治疗药物监测：重点关注影响血药浓度-剂量比的因素。
Therapeutic drug monitoring of perampanel in children diagnosed with epilepsy: Focus on influencing factors on the plasma concentration-to-dose ratio.
机构信息
Department of Pharmacy, Pharmaceutical Sciences Research Center, Children's Hospital of Nanjing Medical University, Nanjing, China.
Institute of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing, China.
出版信息
Epilepsia Open. 2022 Dec;7(4):737-746. doi: 10.1002/epi4.12653. Epub 2022 Oct 12.
OBJECTIVE
This study aimed to investigate the efficacy and tolerability of perampanel (PER) therapy and to optimize a specific plasma reference range for PER in children. Another major aim was to evaluate the potential determinators of PER concentration.
METHODS
Concentrations obtained from 80 children were analyzed for routine therapeutic drug monitoring (TDM) between 2021 and 2022. We retrospectively reviewed the clinical data of these patients and assessed the efficacy at 3 months after treatment initiation. Trough concentration-to-dose ratio (C /Dose ratio) of PER was compared among patients on various potential influencing factors.
RESULTS
A 3-month PER therapy produced a ≥50% reduction in seizure frequency in 58.8% of patients. Twelve patients reported at least one adverse effect (AE), mainly dizziness. The monitoring data showed that the median C was 325.5 ng/mL. Under maintenance dosages, approximately 75% of the C values were 180.0-610.0 ng/mL. The C /Dose ratio in patients aged 1 to <4 was significantly lower by twofold than in those aged 4 to ≤12 years (P = 0.001). Enzyme-inducing ASMs (EIASMs) decreased the C /Dose ratio of PER by 25.9% (P = 0.165). In addition, seizure frequency reduction in responders was achieved at a median PER C value of 357 ng/mL, which was similar to the value of 314 ng/mL found in nonresponders (P = 0.288). No significant difference was found in PER C values between patients with and without AEs (P = 0.082).
SIGNIFICANCE
In this study, PER treatment showed acceptable efficacy and tolerance in Chinese children with epilepsy. Contributing factors like age to variable C /Dose ratios were identified, and complex PER-ASMs interactions were observed. Notably, the reference range, that is, 180.0-610.0 ng/mL, for routine PER monitoring may be more applicable for them. Routine TDM should be considered a positive attempt to manage the effectiveness and safety of PER.
目的
本研究旨在探讨吡仑帕奈（PER）治疗的疗效和耐受性，并为儿童 PER 建立特定的血浆参考范围。另一个主要目的是评估 PER 浓度的潜在决定因素。
方法
对 2021 年至 2022 年期间 80 例儿童进行的常规治疗药物监测（TDM）获得的浓度进行分析。我们回顾性地回顾了这些患者的临床数据，并评估了治疗开始后 3 个月的疗效。比较了不同潜在影响因素下 PER 浓度与剂量比（C /剂量比）。
结果
3 个月 PER 治疗使 58.8%的患者癫痫发作频率降低≥50%。12 名患者报告至少有一次不良反应（AE），主要是头晕。监测数据显示，中位 C 值为 325.5ng/mL。在维持剂量下，约 75%的 C 值为 180.0-610.0ng/mL。年龄为 1 至<4 岁的患者的 C /剂量比明显低至 2 倍（P=0.001）。酶诱导的抗癫痫药（EIASMs）使 PER 的 C /剂量比降低了 25.9%（P=0.165）。此外，在反应者中，PER C 值中位数为 357ng/mL 时达到了癫痫发作频率降低，与无反应者的 314ng/mL 相似（P=0.288）。有和没有 AE 的患者的 PER C 值之间没有显著差异（P=0.082）。
意义
在这项研究中，PER 治疗在中国癫痫儿童中表现出可接受的疗效和耐受性。确定了年龄等可变 C /剂量比的影响因素，并观察到复杂的 PER-ASMs 相互作用。值得注意的是，常规 PER 监测的参考范围，即 180.0-610.0ng/mL，可能更适用于他们。常规 TDM 应被视为管理 PER 有效性和安全性的积极尝试。
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