PPK model
The pharmacokinetics of MPA was best described by a two-compartment linear model with a first-order absorption rate. A mixed model of addition and proportion was used to describe residual variation. The population parameters for Ka, CL, Vc, Vp, and Q were 0.45 h-1, 9.86 L/h, 19.69 L, 408.32 L and 23.01 L/h, respectively. In covariate model, dosage form had a significantly effect on Ka (Figure 2). Cystatin C (CysC) or serum creatinine (Scr) was negatively correlated with CL, while MPO was positively correlated with CL (Figure 3). In addition, MPA showed an extensive tissue distribution (408.32 L) and was significantly correlated with albumin. Simultaneous administration of prednisone statistically influenced on Ka, but did not facilitate an important refinement of model and were discarded during backward elimination. Overall, covariate model decreased inter-individual variability in Ka (from 164.2% to 107.0%), CL (from 101.9% to 74.3%) and Vp(from 112.9% to 70.0%) compared to base model. CysC and MPO provided an explanation of 26.4% and 10.0% of inter-individual variability for CL, respectively (Figure 4).