Pharmacokinetics of free mycophenolic acid and limited sampling strategy for the estimation of area under the curve in liver transplant patients

Abstract

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 AUC0–12h. 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 AUC0–12h was by using C1h, C2h, C4h and C6h. This model showed the minimal mean prediction error and the minimal mean absolute prediction error. In conclusion, the models for estimation of the fMPA AUC0–12h were established in liver transplant recipients and the best model for prediction of fMPA AUC was: estimated fMPA AUC=34.2+1.12C1h+1.29C2h+2.28C4h+3.95C6h.