比较他克莫司缓释制剂与普通制剂在中国肾移植患者的药代动力学  

Comparison the pharmacokinetics of tacrolimus in Chinese kidney transplant patients after repeated-dose of modified release and immediate release preparations

作　　者：张逸凡[1] 陈笑艳[1] 戴晓健[1] 敖建华[2] 钟大放[1] 

机构地区：[1]中国科学院上海药物研究所,上海201203 [2]中国人民解放军总医院,北京100853

出　　处：《中国临床药理学杂志》2011年第9期696-700,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的比较中国肾移植患者重复剂量口服他克莫司(免疫抑制剂)缓释制剂和普通制剂的药代动力学。方法用多中心、随机、开放、平行对照的临床试验。受试者为18～70岁成年初次肾移植患者,按1∶1随机分成他克莫司缓释制剂组,每天1次;普通制剂组,每天2次。患者于术后分别口服他克莫司缓释胶囊,在连续给药后(56±5)d进行24 h的药代动力学比较研究,用液相色谱串联质谱法测定全血中他克莫司浓度。结果术后56 d,他克莫司缓释制剂组(n=17)和普通制剂组(n=15)给药剂量分别为(0.12±0.05)和(0.10±0.04)mg.kg-1.d-1,药代动力学参数tmax分别为(3.10±3.00),(1.80±0.90)h,Cmax分别为(13.20±4.20),(11.80±3.80)ng.mL-1,C24分别为(4.40±1.30),(4.50±1.20)ng.mL-1,AUC0-24分别为(171.70±49.90),(145.10±29.30)ng.mL-1.h。AUC0-24与C24的相关系数,缓释制剂为0.87,普通制剂为0.62。结论初次肾移植患者术后56 d,他克莫司缓释制剂的日剂量比普通制剂高23%,体内暴露量高16%,体内暴露量与谷浓度具有良好的相关性。Objective To compare the pharmacokinetics of tacrolimus in kidney transplant patients treated with modified release and immediate release preparations.Methods It was a multi-centre,open label,1∶1 randomized,parallel,repeated-dose study.Adult kidney transplant recipients aged from 18-70 years were randomized into modified release group once daily（qd） and immediate release group twice a day（bid）.A validated LC/MS/MS method was used to determine blood concentrations of tacrolimus.Results The mean daily dose for modified release（n=17） was（0.12±0.05） mg·kg-1on day 56,and that for immediate release（n=15） was（0.10±0.04） mg·kg-1.The parameters of tacrolimus for the two formulations at steady state were as follows： Cmax was（13.20±4.20） ng·mL-1at（3.10±3.00）h for modified release and（11.80±3.80） ng·mL-1at（1.80±0.90） h for immediate release,C24was（4.40±1.30） and（4.50±1.20） ng·mL-1,and AUC0-24was（171.70±49.90） and（145.10±29.30） ng·mL-1·h,respectively.The coefficient between AUC0-24 and C24 was 0.87 for modified release,and was 0.62 for immediate release,respectively.Conclusion In patients undergoing primary kidney transplantation,daily dose of modified release tacrolimus increases 23% compared with that of immediate release on day 56 after operation,and the systemic exposure to tacrolimus over the 24-hour interval is 16% higher.There is a good correlation between C24 and AUC0-24 for the modified release tacrolimus.

关 键 词：他克莫司缓释制剂 药代动力学 肾移植 

分 类 号：R969.1[医药卫生—药理学] R979.5[医药卫生—药学]