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).