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

作　　者：Zi-cheng YU Pei-jun ZHOU Xiang-hui WANG Bressolle FRANCOISE Da XU Wei-xia ZHANG Bing CHEN 

机构地区：[1]Institute of Clinical Pharmacy and Pharmacology, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China [2]Organ Transplantation Center, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China [3]Laboratoire de Pharmacocinetique Clinique, Faculte de Pharmacie, Universite Montpellier I, Montpellier, France [4]Institute of Clinical Pharmacology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China

出　　处：《Acta Pharmacologica Sinica》2017年第11期1566-1579,共14页中国药理学报（英文版）

基　　金：We thank Prof Terol A and Prof Bataille B for advice and sup- port. This work was supported by the National Natural Science Foundation of China （No 30500626）.

摘　　要：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 Jnterindividual variability Jn the initial volume of distribution （V~/ F）I 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.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 Jnterindividual variability Jn the initial volume of distribution （V~/ F）I 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.

关 键 词：renal transplantation mycophenolate mofetil （MMF） mycophenolic acid （MPA） population pharmacokinetics uridine diphosphate glucuronosyltransferase （UGT） 

分 类 号：R[医药卫生]