喹硫平在中国精神分裂症及情感性障碍患者中的群体药代动力学研究  

Population Pharmacokinetics of Quetiapine in Chinese Patients with Schizophrenia and Affective Disorders

作　　者：刘威[1] 潘姝曼 周婧琪 韩敏钰 曹敏娟[1] 屈昱晨 LIU Wei;PAN Shuman;ZHOU Jingqi;HAN Minyu;CAO Minjuan;QU Yuchen(Department of Pharmacy,Suzhou Psychiatric Hospital,Suzhou 215000,China;Department of Pharmacy,the Second Affiliated Hospital of Suzhou University,Suzhou 215000,China)

机构地区：[1]苏州市广济医院药学部,苏州215000 [2]苏州大学附属第二医院药学部,苏州215000

出　　处：《药学与临床研究》2023年第3期201-206,共6页Pharmaceutical and Clinical Research

基　　金：苏州市科技发展计划(民生科技-医疗卫生应用基础研究SYS2020195);江苏省药学会-奥赛康医院药学科研项目(A202232)。

摘　　要：目的:用非线性混合效应模型(NONMEM)方法建立喹硫平在中国精神分裂症及情感性障碍患者中的群体药代动力学(PPK)模型并研究其影响因素。方法:回顾性收集304例患者的485份血药浓度数据及临床资料,血药浓度为临床常规监测采集的稳态谷浓度。采用NONMEM软件建立中国精神分裂症及情感性障碍患者的群体药代动力学模型,并考察生理指标以及实验室指标等对喹硫平药代动力学参数的影响。采用拟合优度诊断图、自举法(bootstrap)和正态化预测分布误差法(NPDE)进行模型评估。结果:最终模型中喹硫平的表观清除率(CL/F)和表观分布容积(V/F)的群体典型值分别为83 L·h^(-1)和1350 L。协变量分析结果显示年龄对喹硫平的CL/F具有显著性影响,建立的最终模型CL/F参数公式如下:CL/F(L·h^(-1))=83×(AGE/43.1)^(-0.301)。CL/F的个体间变异和残差变异分别为20.8%和11.1%。结论:本研究为首次在中国精神分裂症及情感性障碍患者中开展的喹硫平的群体药代动力学研究,模型验证显示最终模型具有较好的稳定性和可靠性,可为其临床个体化给药提供参考依据。Objective:To establish a population pharmacokinetic(PPK)model of quetiapine and check its possible influencing factors in Chinese patients with schizophrenia and affective disorders by the nonlinear mixed effect model(NONMEM).Methods:A total of 485 quetiapine serum concentrations and clinical data of 304 patients were retrospectively collected.The serum concentrations were the steady-state trough concentrations collected by clinical routine monitoring.A population pharmacokinetic model of Chinese patients with schizophrenia and affective disorders was established using the NONMEM software,and the effects of physiological and laboratory indicators on the pharmacokinetic parameters of quetiapine were investigated.The goodness of fit diagnostic chart,bootstrap and NPDE were used to evaluate the model.Results:The population typical values of apparent clearance rate(CL/F)and the volume of distribution(V/F)were 83 L·h^(-1) and 1350 L,respectively,in the final model.Covariate analysis showed that age had a significant impact on the apparent clearance rate(CL/F)of quetiapine,and the final regression model for quetiapine was as follows:CL/F(L·h^(-1))=83×(AGE/43.1)^(-0.301).The inter-individual variation and residual variation of CL/F were 20.8%and 11.1%,respectively.Conclusion:This study is the first PPK study of quetiapine in Chinese schizophrenics and affective disorders.The model validation results show that the final model has good stability and reliability and can provide reference for its clinical individualized administration.

关 键 词：喹硫平 群体药代动力学 非线性混合效应模型 精神分裂症 情感性障碍 

分 类 号：R969.1[医药卫生—药理学]