CYP3A5*3基因多态性对中国小儿癫痫患者服用培南帕尼药代动力学的影响

IF 1.7 3区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Pharmacogenetics and genomics Pub Date : 2024-08-01 Epub Date: 2024-05-13 DOI:10.1097/FPC.0000000000000535
Ting Zhao, Ji-Rong Feng, Hui-Lan Zhang, Jing Yu, Jie Feng, Ke-Fang Sun, Lu-Hai Yu, Yan Sun, Hong-Jian Li
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引用次数: 0

摘要

目的:本研究首次评估了CYP3A5*3基因多态性对中国儿科癫痫患者血浆中哌仑帕奈(PER)浓度的影响:方法:我们招募了98名患者进行研究。采用液相色谱-串联质谱法测量血浆中 PER 的浓度。标准治疗药物监测的剩余样本被分配用于基因分型分析。疗效的主要衡量标准是在最后一次检查中接受 PER 治疗后癫痫发作的减少率:结果:血浆浓度与每日服用剂量呈线性相关(r = 0.17;P 结论:血浆浓度与每日服用剂量呈线性相关:CYP3A5*3基因的遗传多态性会影响中国儿童癫痫患者的PER血浆浓度。鉴于疗效和潜在毒性与血浆 PER 水平密切相关,因此在为癫痫患者处方 PER 时应考虑 CYP3A5*3 基因的基因型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effects of CYP3A5*3 genetic polymorphisms on the pharmacokinetics of perampanel in Chinese pediatric patients with epilepsy.

Purpose: This study was the first to evaluate the effect of CYP3A5*3 gene polymorphisms on plasma concentration of perampanel (PER) in Chinese pediatric patients with epilepsy.

Methods: We enrolled 98 patients for this investigation. Plasma PER concentrations were measured using liquid chromatography-tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final checkup.

Results: The plasma concentration showed a linear correlation with the daily dose taken ( r  = 0.17; P  < 0.05). The ineffective group showed a significantly lower plasma concentration of PER (490.5 ± 297.1 vs. 633.8 ± 305.5 μg/ml; P  = 0.019). For the mean concentration-to-dose (C/D) ratio, the ineffective group showed a significantly lower C/D ratio of PER (3.2 ± 1.7 vs. 3.8 ± 2.0; P  = 0.040). The CYP3A5*3 CC genotype exhibited the highest average plasma concentration of PER at 562.8 ± 293.9 ng/ml, in contrast to the CT and TT genotypes at 421.1 ± 165.6 ng/ml and 260.0 ± 36.1 ng/ml. The mean plasma PER concentration was significantly higher in the adverse events group (540.8 ± 285.6 vs. 433.0 ± 227.2 ng/ml; P  = 0.042).

Conclusion: The CYP3A5*3 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A5*3 genetic genotype should be factored in when prescribing PER to patients with epilepsy.

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来源期刊
Pharmacogenetics and genomics
Pharmacogenetics and genomics 医学-生物工程与应用微生物
CiteScore
3.20
自引率
3.80%
发文量
47
审稿时长
3 months
期刊介绍: ​​​​Pharmacogenetics and Genomics is devoted to the rapid publication of research papers, brief review articles and short communications on genetic determinants in response to drugs and other chemicals in humans and animals. The Journal brings together papers from the entire spectrum of biomedical research and science, including biochemistry, bioinformatics, clinical pharmacology, clinical pharmacy, epidemiology, genetics, genomics, molecular biology, pharmacology, pharmaceutical sciences, and toxicology. Under a single cover, the Journal provides a forum for all aspects of the genetics and genomics of host response to exogenous chemicals: from the gene to the clinic.
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