吡仑帕奈
四分位间距
癫痫
医学
丙戊酸
CYP3A5
相伴的
CYP3A4型
胃肠病学
内科学
基因型
儿科
不利影响
精神科
生物
遗传学
细胞色素P450
新陈代谢
基因
作者
Huijuan Wang,Junyan Wang,Bin Lin,Huifen Zhang,Yichao Sun,Yuanyuan Wu,Weifeng Ye,Jing Miao
摘要
Abstract Perampanel (PER) is a new type of antiseizure medication used for partial or generalized seizures. However, the plasma concentration shows obvious individual variability in children. The present study aims to ascertain the effect of age, comedications, and cytochrome P450 (CYP) 3A4/5 polymorphisms on PER exposure in Chinese pediatric patients with epilepsy. Clinical data were retrospectively collected in a tertiary children's hospital medical records system from January 2021 to December 2022. The influence factors on the daily dose, plasma concentration, and concentration‐to‐dose ratio (CDR) of PER were investigated. A total of 135 pediatric patients with 178 blood samples were involved. With a median daily dose of 4.0 mg (interquartile range, 3.0‐5.0 mg), the median plasma concentration was 409.4 ng/mL (interquartile range, 251.7‐639.4 ng/mL). The CDR in patients aged less than 4 years was significantly decreased by 48.0% and 39.1% compared with those aged 4‐11 years and 12 years or older, respectively. Enzyme inducers significantly decreased the CDR of PER by 34.5%, while valproic acid showed an increase of 71.7%. In addition, genotype CYP3A5*3/*3 carriers presented a significant increase of 21.5% compared to the CYP3A5*1/*3 expresser. No correlations were observed between the CDR and CYP3A4∗1G polymorphism. PER showed high variations in individual plasma concentrations. Age younger than 4 years, comedication with enzyme inducers or valproic acid, and possession of the CYP3A5*3 genotype potentially predicted PER exposure in pediatric patients with epilepsy.
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