Pharmacokinetics of free mycophenolic acid and limited sampling strategy for the estimation of area under the curve in liver transplant patients.
Mycophenolate Mofetil (MMF) is widely used in preventing acute rejection in liver transplantation. Only free MPA (fMPA) can exert the pharmacological effect. In this study, we aimed to develop the new model which could be best fit to predict the fMPA area under the plasma concentration-time curve (AUC) by limited sampling strategy (LSS) in Chinese liver transplant patients. Fifty patients received MMF with the combination of tacrolimus. Free MPA concentrations were determined around day 7. Optimal subset regression analysis was used to establish the models for estimated fMPA AUC(0-12h). Three excellent better models were validated by Bootstrap analysis. Twenty-four models including four blood time point samplings were established. For the selected four models, 100% were successful and were not significantly different from the original dataset by Bootstrap analysis. The best model for prediction of fMPA AUC(0-12h) was by using C(1h), C(2h), C(4h) and C(6h). This model showed the minimal mean prediction error and the minimal mean absolute prediction error. In conclusion, the models for estimation of the fMPA AUC(0-12h) were established in liver transplant recipients and the best model for prediction of fMPA AUC was: estimated fMPA AUC=34.2+1.12C(1h)+1.29C(2h)+2.28C(4h)+3.95C(6h).
The Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Zhidong
Z
Gu
Bing
B
Chen
Yanyan
Y
Song
Baiyong
B
Shen
Zhecheng
Z
Zhu
Weixia
W
Zhang
Junjie
J
Xie
Xiaxing
X
Deng
Chenghong
C
Peng
Qishi
Q
Fan
Hao
H
Chen
D019540:Area Under Curve; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006084:Graft Rejection / Q000378:metabolism / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000097:blood / Q000493:pharmacokinetics*; D016559:Tacrolimus / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus