Abstract:

ABSTRACT  Objective:  To study the effect of proton pump inhibitors (PPI)  on pharmacokinetical changes of different preparations of mycophenolic acid in kidney transplantation recipients. Methodology: Sixteen renal transplant recipients were randomly divided into group Ⅰ(n=8, treated with mycophenolate mofetil) and group Ⅱ(n=8, treated with EC-MPS). All patients were treated with cyclosporin (sandimmun neoral) and adrenal cortex hormone, and PPI was administrated right after transplantation until the 7th day. The concentration of MPA, Tmax and Cmax were observed in the 3rd, 7th and 10th day. 1 ml blood was sampled before and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h after drug administration. The plasma concentration of MPA was determined by HPLC-UV detection and the pharmacokinetic parameters were calculated by WinNonlin 5.2 using non-compartment model. Results: The main pharmacokinetic parameters were as follows: For group 1, Tmax was 1.50±0.71, 2.50±1.04, 1.25±0.60 (h) respectively on the 3rd, 7th and 10th day, Cmax was 7.69±2.25, 8.95±5.60, 9.87±3.82 (ug/ml) (P>0.05), and MPA-AUC0-12h was 38.9±14.6, 34.6±12.0, 32.5±10.8 (mg.h.L-1) (P=0.325). For group 2, Tmax was 2.50±0.53, 2.56±0.62, 2.63±0.74 (h) (P=0.939) on the 3rd, 7th and 10th day, Cmax was 11.6±9.59, 12.6±8.49, 10.1±9.19 (ug/ml) respectively (P=0.687), and MPA-AUC0-12h was 22.8±15.5, 25.3±10.4, 16.7±14.8 (mg.h.L-1) (P=0.197). P value of MPA-AUC0-12h between the two groups was 0.065, 0.382 and 0.05 on the 3rd, 7th and 10th day, tmax was 0.01, 0.721 and 0.002 respectively, and Cmax was 0.878, 0.328 and 0.505.  Conclusion: The Tmax of MMF was increased significantly with the use of PPI, and the Cmax of MMF showed some downward trend. However, PPI showed little effect on the pharmacokinetics of EC-MPS. MPA concentration should be detected early after transplantation in patients using MMF as immunosuppressant and the dose of MMF can be adjusted timely accordingly.

Key words:  kidney transplantation , proton pump inhibitors , mycophenolic acid