细胞色素P450 3A5和多药耐药基因遗传变异的联合效应对克拉霉素药代动力学的影响  

Combined effect of CYP3A5 and multidrug resistance gene 1 genetic variations on pharmacokinetics of clarithromycin

作　　者：储小曼[1] 曹晓梅[1] 倪立[1] 姚旋[1] 周琰[2] 

机构地区：[1]南京军区南京总医院药理科,南京210002 [2]南京医科大学药学院

出　　处：《中国临床药理学杂志》2009年第5期412-417,共6页The Chinese Journal of Clinical Pharmacology

基　　金：南京市科技计划基金资助项目(200802051)

摘　　要：目的观察CYP3A5*3和MDR1 C3435T遗传变异的联合效应对中国健康受试者克拉霉素(大环内酯类抗生素)药代动力学的影响。方法45名受试者服用单剂量克拉霉素胶囊250mg,HPLC-MS法测定血药浓度。PCR-ASA法和PCR-RFLP法分别测定受试者CYP3A5*3和MDR1 C3435T的基因型,按基因型分组,比较基因多态性对克拉霉素药代动力学的影响。结果在45名受试者中,CYP3A5*3各基因型分布,不受MDR1 C3435T基因型的影响;而2者的基因突变均不同程度地协同影响克拉霉素药代动力学参数Cmax、AUC0-24和tmax。结论CYP3A5*3和MDR1C3435T遗传变异及协同作用是影响克拉霉素药代动力学特性的重要因素。Objective To investigate whether the CYP3A5＊3 and multidrug resistance gene （MDR1 ） C3435T polymorphism would affect clarithromycin pharmacokinetics in Chinese healthy volunteers. Methods With the blood samples from 45 Chinese healthy male volunteers,CYP3A5＊3 genotype and MDR1 C3435T genotype were respectively determined by PCR-ASA and PCR-RFLP,and clarithromycin concentrations were measured by HPLC-MS assay. Pharmacokinetic analysis was performed to assess the effect of genotype on clarithromycin pharmacokinetics. Results According to these 45 volunteers, there was not correlation between CYP3A5 ＊ 3 and MDR1 C3435T genotyp distribution frequencies, while the mutations of both influenced the pharmacokinetic parameters C AUC0-24 and tmax cooperatively but to different extents. Conclusion The result of this study suggested that mutation in CYP3A5 ＊ 3 and MDR1 C3435T may influence the pharmacokinetics of clatithromycin together.

关 键 词：细胞色素P4503A5＊3 多药耐药基因 克拉霉素 遗传变异 药代动力学 

分 类 号：R978.15[医药卫生—药品] R969.1[医药卫生—药学]