Pharmacokinetics of enteric-coated mycophenolate sodium in Chinese renal transplantation recipients

Background Mycophenolic acid（MPA） as an anti-proliferative immune-suppressive agent is used in the majority of immunosuppressive regimens in solid organ transplantation.This study aimed to investigate the pharmacokinetic（PK） characteristics of enteric-coated mycophenolate sodium（EC-MPS） and area under the curve（AUC） from 0 to 12 hours with limited sampling strategies（LSSs） in Chinese renal transplant recipients. Methods This study was conducted in 10 Chinese renal transplant patients receiving living donor and treated with EC-MPS,cyclosporine,and corticosteroids.MPA concentrations were measured by enzyme multiplied immunoassay technique（EMIT）.Whole 12-hour PK profiles were obtained on Day 4 after operation.LSSs with jackknife technique, multiple stepwise regression analysis,and Bland-Altman analysis were developed to estimate MPAAUC. Results The mean maximum plasma concentration,the mean time for it to reach peak(T;),and the mean MPA AUC were（11.38±2.49） mg/L,（4.85±3.32） hours,and（63.19±13.54） mgh·L;,respectively.Among the 10 profiles,MPA AUC of four patients was significantly higher than that of the other six patients,and the corresponding T;was significantly longer than that of the other six patients.No patient exhibited a second peak caused by enterohepatic recirculation.The best models were as follows-.27.46±0.94C;±3.24C;±2.81C;（r;=0.972）,which was used to predict AUC of fast metabolizer with a mean prediction error（MPE） of -0.21%and a mean absolute prediction error（MAE） of 2.59%; 36.65±3.08C;±5.30C;-4.04C;（r;=0.992）,which was used to predict AUC of slow metabolizer with a MPE of 0.58%and a MAE of 1.95%. Conclusions The PKs of EC-MPS had a high variability among Chinese renal transplant recipients.The preliminary PK data indicated the existence of slow and fast metabolizer.These findings may be associated with the enterohepatic recirculation.