  AIMS A population pharmacokinetic (PK) analysis was performed to: (1)
characterise the PK of unbound and total mycophenolic acid (MPA) and its
7-O-mycophenolic acid glucuronide (MPAG) metabolite, and (2) identify the
clinically significant covariates that cause variability in the dose-exposure
relationship to facilitate dose optimisation. METHODS A total of 740 unbound
MPA (uMPA), 741 total MPA (tMPA) and 734 total MPAG (tMPAG) concentration-time
data from 58 Chinese kidney transplant patients were analysed using a nonlinear
mixed-effect model. The influence of covariates was tested using a stepwise
procedure. RESULTS The PK of unbound MPA and MPAG were characterised by a two-
and one-compartment model with first-order elimination, respectively. Apparent
clearance of uMPA (CLuMPA/F) was estimated to be 852 L/h with a relative
standard error (RSE) of 7.1%. The tMPA and uMPA were connected using a linear
protein binding model, in which the protein binding rate constant (kB)
increased non-linearly with the serum albumin (ALB) concentration. The
estimated kB was 53.4 /h (RSE, 2.3%) for patients with ALB of 40 g/L. In
addition, model-based simulation showed that changes in ALB substantially
affected tMPA but not uMPA exposure. CONCLUSIONS The established model
adequately described the population PK characteristics of the uMPA, tMPA, and
MPAG. The estimated CLuMPA/F and unbound fraction of MPA (FUMPA) in Chinese
kidney transplant recipients were comparable to those published previously in
Caucasians. We recommend monitoring uMPA instead of tMPA to optimise
mycophenolate mofetil (MMF) dosing for patients with lower ALB levels.
