The relationship between Aripiprazole metabolic ratio and CYP2D6 gene polymorphism in children with tic disorders and its influence on dose-exposure
10.3760/cma.j.cn101070-20240401-00193
- VernacularTitle:抽动障碍儿童的阿立哌唑代谢比与 CYP2D6基因多态性的关系及对剂量-暴露的影响
- Author:
Huimin CHEN
1
;
Yang WANG
;
Liuliu GAO
;
Zhisheng LIU
Author Information
1. 华中科技大学同济医学院附属武汉儿童医院神经内科，武汉 430016
- Keywords:
Child;
Tic disorders;
Aripiprazole;
Dehydroaripiprazole;
Metabolic ratio;
CYP2D6
- From:
Chinese Journal of Applied Clinical Pediatrics
2024;39(11):842-847
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the relationship between the in vivo metabolic ratio (MR) of Aripiprazole (ARI) and CYP2D6 gene polymorphism in children with tic disorders (TD) and its effect on dose-exposure (DE), so as to promote precision drug use. Methods:In this study, a real-world observational study design was used to collect 81 children with TD who visited the Department of Neurology of Wuhan Children′s Hospital from January 2021 to January 2024, the concentration of the prototype drug and the main metabolite Dehydroaripiprazole (DARI), the detection data of CYP2D6 single nucleotide gene polymorphism (SNP) and clinical data were collected, and the relationship between the DARI/ARI metabolic ratio (MR) and CYP2D6 metabolic type was analyzed by the receiver operating characteristic (ROC) curve.A DE model between ARI dose and steady-state trough concentration was established by population modeling, and the effects of CYP2D6 metabolic type, MR and body weight on DE were analyzed.Goodness-of-fit diagram (GOF), visual predictive check (VPC) and prediction error analysis were used to verify the prediction performance of the DE model.Results:ROC analysis showed that there was a correlation between MR and CYP2D6 metabolic type, the MR sensitivity cut-point of CYP2D6 ultrafast metabolic (UM) patients was 0.399, and the cut-point of MR in intermediate metabolic (IM) patients was 0.252.Based on this, the patients were divided into three categories: MR TYPE Ⅰ: MR≥0.399, MR TYPE Ⅱ: 0.252
