Pharmacokinetic and pharmacodynamic studies of mycophenolic acid in renal transplant recipients

The purpose was to identify the pharmacokinetic and pharmacodynamic profiles, to establish the PK-PD relationship of MPA and to quantify average population pharmacokinetic and pharmacodynamic parameters and evaluate the influence covariates on the PK-PD variability.Stable renal transplant patients who were on mycophenolate mofetil/sirolimus/steroids, for conventional study (n=6) and for the PK-PD modeling (n=46), were included.The mean total Cmax and AUC were 11.99B17.22 mg/L and 46.81B121.44 mg.h/L respectively. The free fraction of MPA was ranged from 0.4-1.06%. The mean percent inhibition of IMPDH activity at Cmin and Cmax were 13.05B116.45 and 67.24B115.56% respectively.Structure basic and final model for PK and PD were developed using non linear mixed effects modeling. White blood cell count appeared to be the sole important covariate affecting the IC50 of free MPA, substantially reducing inter-individual variation in this PD parameter by 5.3% and intra-individual variation by 25.47%.This study confirmed that patients taking MMF and SRL experience a higher exposure to MPA and lower exposure to MPAG and the population PK-PD model developed in this study may allow for accurate prediction of individualb s response.

Author dc:creator

• NWAY NWAY AYE

• pharmacokinetic, pharmacodynamic, mycophenolate mofetil, mycophenolic acid, modeling