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 MPA AUC. Results The mean maximum plasma concentration, the mean time for it to reach peak (T-max), and the mean MPA AUC were (11.38 +/- 2.49) mg/L, (4.85 +/- 3.32) hours, and (63.19 +/- 13.54) mg.h.L-1, respectively. Among the 10 profiles, MPA AUC of four patients was significantly higher than that of the other six patients, and the corresponding T-max 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)+3.24C(8)+2.81C(10) (r(2)=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(8)+5.30C(10)-4.04C(12) (r(2)=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. Chin Med J 2012;125(23):4226-4232