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Influences of CYP2D6*10 polymorphisms on the pharmacokinetics of iloperidone and its metabolites in Chinese patients with schizophrenia: a population pharmacokinetic analysis 期刊论文

编号：

36BA462B93CACE93EC2B09B8DEB106E7
作者：

Pei, Qi(裴奇)#^[1,2]Huang, Lu#^[1,2]Huang, Jie(黄洁)^[1,2]Gu, Jingkai(顾景凯)^[3]Kuang, Yun^[1,2];Zuo, Xiaocong(左笑丛)^[1,2]Ding, Junjie^[4];Tan, Hongyi(谭鸿毅)^[1,2]Guo, Chengxian(郭成贤)^[1,2]Liu, Shikun(刘世坤)*^[1,2]Yang, Guoping(阳国平)*^[1,2]
语种：

英文
期刊：

ACTA PHARMACOLOGICA SINICA ISSN：1671-4083 2016 年 37 卷 11 期 (1499 - 1508) ; NOV
收录：
关键词：

schizophrenia iloperidone gene polymorphisms CYP2D6*10 population pharmacokinetics
摘要：

Aim: Iloperidone is an atypical antipsychotic drug that is mainly metabolized by CYP2D6, CYP3A4, and cytosolic enzymes. Previous studies show that extensive and poor metabolizers of CYP2D6 exhibit different plasma concentrations of iloperidone and its metabolites. The aim of this study was to develop a parent-metabolite population pharmacokinetic (PPK) model to quantify the effects of CYP2D6*10 allele on the pharmacokinetics of iloperidone and its metabolites in Chinese schizophrenia patients. Methods: Seventy Chinese schizophrenia patients were enrolled, from whom limited blood samples were collected on d 15 (0 h) and d 28 (0, 4 and 12 h after drug administration). The plasma concentrations of iloperidone and its metabolites M-1 (P-88) and M-2 (P-95) were simultaneously detected using a validated HPLC-MS assay. CYP2D6*10 (rs1065852) genotyping was performed. A PPK model was developed based on data from the patients using the NONMEM software (version 7.2). A one-compartment model with first-order absorption and elimination was used to describe the pharmacokinetic data related to iloperidone and its metabolites. Results: Patients with the CYP2D6*10 T/T genotype had significantly higher concentrations of iloperidone and M1, and lower concentrations of M2 than the patients with C/C or C/T genotypes. The CYP2D6*10 genotype affected the elimination constants for transformation of iloperidone to the metabolites M-1 (K-23) and M-2 (K-24). The K-23 value of the patients with T/T genotype was 1.34-fold as great as that of the patients with C/C or C/T genotype. The K-24 value of the patients with C/T and T/T genotypes was 0.693- and 0.492-fold, respectively, as low as that of the patients with C/C genotype. Conclusion: CYP2D6*10 mutations affect the pharmacokinetics of iloperidone and its metabolites in Chinese schizophrenia patients, suggesting that the clinical doses of iloperidone for patients with CYP2D6*10 mutations need to be optimized.
推荐引用方式
GB/T 7714：

Pei Qi,Huang Lu,Huang Jie, et al. Influences of CYP2D6*10 polymorphisms on the pharmacokinetics of iloperidone and its metabolites in Chinese patients with schizophrenia: a population pharmacokinetic analysis [J].ACTA PHARMACOLOGICA SINICA,2016,37(11):1499-1508.
APA：

Pei Qi,Huang Lu,Huang Jie,Gu Jing-kai,&Yang Guo-ping.(2016).Influences of CYP2D6*10 polymorphisms on the pharmacokinetics of iloperidone and its metabolites in Chinese patients with schizophrenia: a population pharmacokinetic analysis .ACTA PHARMACOLOGICA SINICA,37(11):1499-1508.
MLA：

Pei Qi, et al. "Influences of CYP2D6*10 polymorphisms on the pharmacokinetics of iloperidone and its metabolites in Chinese patients with schizophrenia: a population pharmacokinetic analysis" .ACTA PHARMACOLOGICA SINICA 37,11(2016):1499-1508.
入库时间：

1/20/2022 4:05:30 PM
更新时间：

1/20/2022 4:05:30 PM
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