拉考沙胺
CYP2C19型
药代动力学
药效学
医学
药理学
药物遗传学
内科学
不利影响
癫痫
基因型
胃肠病学
单核苷酸多态性
CYP2D6型
SLCO1B1型
静脉血
生物
细胞色素P450
新陈代谢
遗传学
基因
精神科
作者
Seon‐Jae Ahn,Jaeseong Oh,Do‐Yong Kim,Hyoshin Son,Sungeun Hwang,Hye‐Rim Shin,Eun Young Kim,Han Sang Lee,Woo‐Jin Lee,Jangsup Moon,Soon‐Tae Lee,Keun‐Hwa Jung,Kyung‐Il Park,Ki‐Young Jung,SeungHwan Lee,Kyung‐Sang Yu,Kon Chu,Sang Kun Lee
出处
期刊:Epilepsia
[Wiley]
日期:2022-08-21
卷期号:63 (11): 2958-2969
被引量:10
摘要
Many pharmacokinetic studies of lacosamide (LCM) have been reported, but no large-scale clinical study has been conducted on genetic polymorphisms that affect the metabolism of LCM. Therefore, we designed a pharmacogenetic study of LCM to explore the effect of genetic polymorphisms on serum LCM concentration. We evaluated the pharmacodynamic characteristics of LCM, including clinical efficacy and toxicity.Adult patients with epilepsy who received LCM at Seoul National University Hospital were enrolled. Blood samples were obtained from 115 patients taking LCM for more than 1 month with unchanged doses and were used to analyze the serum LCM concentration, the concentration/dose (C/D) ratio and the single nucleotide polymorphisms (SNPs) of the cytochrome P450 (CYP)2C9 and CYP2C19 genes. In addition, clinical information-including efficacy, toxicity, and concomitant drugs-was collected.The serum LCM concentration showed a linear correlation with the daily dose (r = .66, p < .001). In genetic analysis, 43 patients (38.7%) were extensive metabolizers (EMs), 51 (45.9%) were intermediate metabolizers (IMs), and 17 (15.3%) were poor metabolizers (PMs). In the group comparison, mean serum concentrations and the C/D ratio showed significant differences between the three groups (p = .01 and p < .001, respectively). The C/D ratios of IM (27.78) and PM (35.6) were 13% and 39% higher than those of EM (25.58), respectively. In the pharmacodynamic subgroup analysis, patients in the ineffective LCM group had significantly lower serum concentrations (6.39 ± 3.25 vs. 8.44 ± 3.68 μg/ml, p = .024), whereas patients with adverse events had higher serum concentrations than those without adverse events (11.03 ± 4.32 vs. 7.4 ± 3.1 μg/ml, p < .001). Based on this, we suggest a reference range for LCM in the Korean population (6-9 μg/ml).Genetic polymorphisms of the CYP2C19 gene affect the serum LCM concentration. Because efficacy and toxicity are apparently related to serum LCM levels, the genetic phenotype of CYP2C19 should be considered when prescribing LCM for patients with epilepsy.
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