Pharmacokinetics of tacrolimus converted from twice-daily formulation to once-daily formulation in Chinese stable liver transplant recipients  

作　　者：Yi-fan ZHANG Xiao-yan CHEN Xiao-jian DAI Xi-sheng LENG Da-fang ZHONG 

机构地区：[1]Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China [2]Peking University People＇s Hospital, Beijing 100044, China

出　　处：《Acta Pharmacologica Sinica》2011年第11期1419-1423,共5页中国药理学报（英文版）

摘　　要：Aim： To evaluate the pharmacokinetics of tacrolimus in Chinese stable liver transplant recipients converted from immediate release （IR） tacrolimus-based immunosuppression to modified release （MR） tacrolimus-based immunosuppression. Methods： Open-label, multi-center study with a one-way conversion design was conducted. Eighty-three stable liver recipients （6-24 months post-transplant） with normal renal and stable hepatic function were converted from IR tacrolimus twice-daily treatment to MR tacrolimus once-daily treatment on a 1：1 （mg：mg） total daily dose basis. Twenty-four hour pharmacokinetic studies were carried out on d 0 （pre-conversion）, d 1, and d 84 （post-conversion）. Results： The area under the blood concentration-time curve of MR tacrolimus from 0 to 24 h （AUC0-24） on d I was comparable to that of IR tacrolimus on d0, with a 90% confidence interval （CI） for MR/IR tacrolimus of 92%-97%. The AUC0-24 value for MR tacrolimus on d 84 with the daily dose increased by 14% was approximately 17% lower than that for IR tacrolimus. The 90% CI was 77%-90%, outside the bioequivalence range of 80%-125%. There was a good correlation between AUC0-24 and concentration at 24 h （C24） for IR tacrolimus （d 0, r=0.930） and MR tacrolimus （d 1, r=0.936; d 84, r=0.903）. Conclusion： The exposure to tacrolimus when administered MR tacrolimus once daily is not equivalent to that for IR tacrolimus twice daily after an 84-day conversion in Chinese stable liver transplant recipients. The dose should be adjusted on the basis of trough levels. The therapeutic drug monitoring for patients treated with IR tacrolimus is considered to be applicable to MR tacrolimus.Aim： To evaluate the pharmacokinetics of tacrolimus in Chinese stable liver transplant recipients converted from immediate release （IR） tacrolimus-based immunosuppression to modified release （MR） tacrolimus-based immunosuppression. Methods： Open-label, multi-center study with a one-way conversion design was conducted. Eighty-three stable liver recipients （6-24 months post-transplant） with normal renal and stable hepatic function were converted from IR tacrolimus twice-daily treatment to MR tacrolimus once-daily treatment on a 1：1 （mg：mg） total daily dose basis. Twenty-four hour pharmacokinetic studies were carried out on d 0 （pre-conversion）, d 1, and d 84 （post-conversion）. Results： The area under the blood concentration-time curve of MR tacrolimus from 0 to 24 h （AUC0-24） on d I was comparable to that of IR tacrolimus on d0, with a 90% confidence interval （CI） for MR/IR tacrolimus of 92%-97%. The AUC0-24 value for MR tacrolimus on d 84 with the daily dose increased by 14% was approximately 17% lower than that for IR tacrolimus. The 90% CI was 77%-90%, outside the bioequivalence range of 80%-125%. There was a good correlation between AUC0-24 and concentration at 24 h （C24） for IR tacrolimus （d 0, r=0.930） and MR tacrolimus （d 1, r=0.936; d 84, r=0.903）. Conclusion： The exposure to tacrolimus when administered MR tacrolimus once daily is not equivalent to that for IR tacrolimus twice daily after an 84-day conversion in Chinese stable liver transplant recipients. The dose should be adjusted on the basis of trough levels. The therapeutic drug monitoring for patients treated with IR tacrolimus is considered to be applicable to MR tacrolimus.

关 键 词：TACROLIMUS modified release clinical pharmacokinetics liver transplantation 

分 类 号：S859.796[农业科学—临床兽医学] Q813[农业科学—兽医学]