麦考酚酸在大鼠体内的肠肝循环模型  

Enterohepatic circulation of mycophenolic acid in rat models

作　　者：夏琴[1] 姜慧婷[1] 支建明[2] 陈冰[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院药剂科,上海200025 [2]上海交通大学医学院生理学教研室,上海200025

出　　处：《药学服务与研究》2018年第1期21-25,共5页Pharmaceutical Care and Research

摘　　要：目的:研究麦考酚酸(mycophenolic acid,MPA)在大鼠体内的肠肝循环过程。方法:5只雄性SD大鼠静脉注射MPA,收集0~12h的全血标本,测定MPA浓度。5只雄性大鼠静脉注射给予MPA,收集0~12h的胆汁标本,测定MPA和7-O-葡糖苷酸麦考酚酸(MPAG)浓度。采用10对雄性SD大鼠建立大鼠肠肝循环模型,测定供体和受体大鼠0~12h的MPA的血药浓度。结果:大鼠静脉注射MPA 20mg/kg后AUC0~12h为(43.3±20.4)μg·h·ml-1,给药后8h出现吸收峰。大鼠胆汁实验中,MPA在0~0.33h、0.33~0.67h、0.67~1h、1~1.5h、1.5~2h、2~4h、4~8h、8~12h随胆汁排出量为0.078、0.077、0.049、0.062、0.079、0.114、0.120、0.073mg。胆汁供体组和胆汁受体组大鼠MPA的AUC0~12h分别是(42.3±27.1)和(4.28±3.05)μg·h·ml-1,胆汁受体组大鼠在接收胆汁后8h血药浓度达到峰值。结论:约有10%的MPA进行肠肝循环被重吸收,与人体内过程基本一致;大鼠肠肝循环模型中肠肝循环的峰值在给药后的6~8h。Objective：To study the enterohepatic circulation of mycophenolic acid（MPA）in rats.Methods：Five male SD rats were intravenously injected with MPA.Whole blood samples 0-12 hafter medication was collected,and plasma concentrations of MPA were determined.Five male SD rats were intravenously injected with MPA,the bile samples 0-12 hlater were collected,and concentrations of MPA and 7-O-glucuronide conjugate of MPA（MPAG）were determined.The rat model of enterohepatic circulation was established by using 10 pairs of male SD rats and MPA plasma concentrations of donor and recipient rats0-12 hlater were also determined.Results：The AUC0-12 hof MPA was（43.3±20.4）μg·h·ml-1 after intravenous injection of MPA 20 mg/kg.There was a peak at hour 8 after MPA administration.In the rat bile test,the excretion rates of MPA from bile were 0.078,0.077,0.049,0.062,0.079,0.114,0.120,0.073 mg respectively at the time points of 0 to 0.33 h,0.33 to 0.67 h,0.67 to 1 h,1 to 1.5 h,1.5 to 2 h,2 to 4 h,4 to 8 h,8 to 12 h.AUC0-12 hof MPA for bile-donor rats and bile-recipient rats were（42.3±27.1）and（4.28±3.05）μg·h·ml-1,respectively.There was a peak concentration of MPA in recipient rats at hour 8 after bile transferred.Conclusion：About 10% of MPA was reabsorbed in enterohepatic circulation,which is consistent with the process in the human body.The peak value of MPA in enterohepatic circulation in the rat model was 6-8 h after administration of MPA.

关 键 词：麦考酚酸 肠肝循环 药动学 大鼠 

分 类 号：R965[医药卫生—药理学] R979.5[医药卫生—药学]