Clinical drug-drug interactions（DDIs） induced by CYP3A may reduce the exposure and pharmacological activity of CYP3A substrate.Up-regulation of CYP3A mRNA is often used to evaluate inductive effect of test compounds on CYP3A. A quantitative real time PCR assay was developed and validated for the absolute quantification of CYP3A1 and CYP3A2 mRNA.Specific primers of CYP3A1,CYP3A2 and GAPDH（glyceraldehyde-3-phosphate dehydrogenase,as a house-keeping gene） were well designed.The relationship between threshold cycle（Ct） and logarithm of the concentrations of CYP3A1, CYP3A2 and GAPDH was linear ranged from 1 attomol/μL to 1×10~6 attomol/uL with great inter- and intra-assay reproducibility. This method was successfully applied to investigate the time courses of CYP3A1 and CYP3A2 mRNA induction in rat liver after 100 mg/kg dexamethasone（DEX） administration by intraperitoneal（i.p.） injection.The baseline levels of CYP3A1 and CYP3A2 mRNAs were 37.78 attomol/ug（total RNA） and 252.31 attomol/ug（total RNA）,respectively.CYP3A1 and CYP3A2 mRNA values increased gradually to their peak levels（19- and 8- fold vs.baseline） within 24 h and 42 h,respectively,and then returned to their baseline 60 h after DEX administration.
构建中国肾移植患者他克莫司治疗药物监测网络平台,方便医生管理患者信息,并且为患者提供群体、亚群体和个体3个不同层次的治疗药物监测。通过使用数据库管理系统MySQL软件建立和管理医生信息数据库以及患者信息数据库,使用超文本标记语言(hypertext mark-up language,HTML)和Java语言的JSP(Java server pages)技术研制患者信息数据库的网络管理平台,为医生提供数据库管理功能;在已建立好的群体药物动力学模型的基础上,运用以上编程语言研制群体和亚群体预测功能模块;根据贝叶斯原理和最大后验概率密度函数,建立目标函数,选择最优化算法,研制个体预测功能模块。网络平台能够为医生提供管理患者数据库功能和3个水平的预测功能,为肾移植患者服用他克莫司个体化给药提供指导,并为其他药物的治疗药物监测网络平台的研制提供模板。
