奎硫平
富马酸奎硫平
药代动力学
人口
奥氮平
双相情感障碍
医学
CYP2D6型
内科学
治疗药物监测
精神科
药理学
非定型抗精神病薬
精神分裂症(面向对象编程)
抗精神病药
心情
细胞色素P450
环境卫生
新陈代谢
作者
Meihua Lin,Yu Zhang,Duo Lv,Nana Xu,Xi Yang,Xueling Liu,Caixia Yan,Meijia Wu,Jiejing Kai,Shaohua Hu,Qingwei Zhao
标识
DOI:10.1016/j.jad.2024.01.170
摘要
There is great interindividual difference in the plasma concentration of quetiapine, and optimizing quetiapine therapy to achieve a balance between efficacy and safety is still a challenge. In our study, a population pharmacokinetic (PPK) model considering genetic information was developed with the expectation of comprehensively explaining this observation in Chinese patients with bipolar disorder. Patients who were dispensed quetiapine and underwent the therapeutic drug monitoring (TDM) were included. The genotypes of CYP3A5*3, CYP2D6*10, and ABCB1 C3435T/G2677T were analyzed. Finally, a multivariable linear regression model was applied to describe the PPK of quetiapine considering the covariates weight, height and genotype information. A total of 175 TDM points from 107 patients were adopted for PPK model development. Resultantly, the CL/F of quetiapine in CYP3A5 expressers was 81.1 CL/h, whereas it was 43.6 CL/h in CYP3A5 nonexpressers. The interindividual variability in CL/F was 47.7 %. However, neither the ABCB1 nor CYP2D6 genotype was significantly associated with the predictor of quetiapine clearance in our study. Only trough concentrations were collected, and the span between different points was relatively wide, impeding the application of the typical nonlinear compartment model for PPK analysis. In addition, this was a single-center study which limited the sample of wild-type CYP3A5 carriers. The currently established PPK model of quetiapine considering the contribution of the CYP3A5 genotype could efficiently predict the population and individual pharmacokinetic parameters of Chinese bipolar disorder patients, which could better guide the personalized therapy with quetiapine, thus to achieve the best clinical response.
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