Original Article

Population pharmacokinetics and Bayesian estimation of mycophenolic acid concentrations in Chinese adult renal transplant recipients

Authors: YU Zi-cheng, ZHOU Pei-jun, WANG Xiang-hui, FRANҪOISE Bressolle, XU Da, ZHANG Wei-xia, CHEN Bing
Corresponding to: YU Zi-cheng
DOI: 10.1038/aps.2017.115

Abstract

Mycophenolate mofetil (MMF) is an important immunosuppressant used in renal transplantation, and mycophenolic acid (MPA) is the active component released from the ester prodrug MMF. The objective of this study was to investigate the population pharmacokinetics of mycophenolic acid (MPA) following oral administration of MMF in Chinese adult renal transplant recipients and to identify factors that explain MPA pharmacokinetic variability. Pharmacokinetic data for MPA and covariate information were retrospectively collected from 118 patients (79 patients were assigned to the group for building the population pharmacokinetic model, while 39 patients were assigned to the validation group). Population pharmacokinetic data analysis was performed using the NONMEM software. The pharmacokinetics of MPA was best described by a two-compartment model with a first-order absorption rate with no lag time. Body weight and serum creatinine level were positively correlated with apparent clearance (CL/F). The polymorphism in uridine diphosphate glucuronosyltransferase gene, UGT2B7, significantly explained the interindividual variability in the initial volume of distribution (V1/ F). The estimated population parameters (and interindividual variability) were CL/F 18.3 L/h (34.2%) and V1/F 27.9 L (21.3%). The interoccasion variability was 13.7%. These population pharmacokinetic data have significant clinical value for the individualization of MMF therapy in Chinese adult renal transplant patients.
Keywords: renal transplantation; mycophenolate mofetil (MMF); mycophenolic acid (MPA); population pharmacokinetics; uridine diphosphate glucuronosyltransferase (UGT)