他克莫司在肝移植患者体内的药动学  

Study on the pharmacokinetics of tacrolimus in recipients of liver transplantation

作　　者：张弋[1] 付鹏[1] 郑虹[1] 朱志军[1] 沈中阳[1] 芮建中[2] 娄建石[3] 

机构地区：[1]天津市第一中心医院药剂科,天津300192 [2]南京军区总医院药理科,江苏南京210002 [3]天津医科大学,天津300070

出　　处：《中国医院药学杂志》2008年第16期1338-1341,共4页Chinese Journal of Hospital Pharmacy

基　　金：天津市卫生局课题(编号:局02KY15)

摘　　要：目的:考察口服他克莫司(FK506)胶囊在肝移植患者体内的药动学特征,为临床调整个体化给药方案提供科学依据。方法:22例肝移植患者,给予FK506为基础的免疫抑制治疗,术后24h后开始服用FK506,剂量为(0.13±0.04)mg·kg-1·d-1,每12h服用1次。受试者在服药前(0h)和服药后0.33,0.66,1,1.5,2,3,4,6,8,10,12h共12个时间点分别取外周静脉血,用MEIA法进行药物浓度测定,PKBP-N1软件计算药动学参数,并绘制血药浓度-时间曲线。结果:FK506口服后血药浓度-时间曲线为一级吸收二室开放模型,22例肝移植受者在口服FK506后,血药浓度迅速上升达到峰值,然后迅速下降,PK参数分别为t1/2α为(1.2±2.1)h,t1/2β(21.0±10.1)h,Ka(2.2±0.9)·h-1,CLs为(0.6±0.3)L·h-1·kg-1,AUC0-12为(136.2±33.7)μg·h·L-1。本实验中和AUC相关性最好的是C3、C4、C8,r分别为0.95,0.94,0.91。结论:肝移植患者口服FK506药动学个体差异大,用药应个体化。根据PKBP-N1分析得到的药动学参数,能较好的体现患者的药动学信息,根据单点血药浓度可以比较准确的预测AUC0-12。OBJECTIVE To evaluate pharmacokinetic characteristics of tacrolimus （FK506） orally administered from routing therapeutic drug monitoring in liver transplant recipients for improving the project of individual dosage. METHODS The 22 recipients after liver transplantation were given with FK506-based immunosuppressive scheme 24 hours after surgery. To analyse FK506 levels, blood samples were taken from vein into EDTA tube at 0,0. 33,0.66,1,1.5,2,3,4,6,8, 10, 12 h. The whole blood concentration was measured by MEIA. The pharmacokinetic parameters were calculated and the C-T curves were depicted by PKBP-N1 program. RESULTS C-T curves showed two-compartment open model of pharmacokinetics in the steady state after oral FK506. The pharmacokinetic parameters of FKS06 for 22 patients were as follows respectively： tmax = 0. 66 - 2 h,Cmax = 15. 1 -40 μg·L^-1 ,t1/2α = （1.22 ± 2. 10）h,t1/2β = （21.04± 10. 11）h,Ka = （2. 18 ±0. 91）·h-1 ,CLs = （0. 56 ±0.34）L·h^-1 ·kg^-1 , AUC0-12= （136. 2 ±33. 7）μg· h· L^-1. There were relative good relation between Cmin, and AUC0-12 （r = 0. 82）, whereas the better relations was between C3 and AUC0- 12 （r = 0. 95）, between C4 and AUG0- 12 （ r = 0.94）, between C8 and AUC0-12 （r = 0. 91 ）. Two-compartment model fitted was better than one-compartment model in routine monitoring steady-state trough concentration of FK506. CONCLUSION FK506 is an effective immunosuppressant for liver transplantation. There is great individual difference. The pharmacokinetic parameters analyzed by PKBP-N1 could represent the individual pharmacokinetic information. Abbreviation AUC could be accurately predicted by single point concentration.

关 键 词：他克莫司 药动学 肝移植 微粒子酶免疫法 

分 类 号：R969.1[医药卫生—药理学]