Nonlinear relationship between enteric-coated mycophenolate sodium dose and mycophenolic acid exposure in Han kidney transplantation recipients

The aim of the research was to investigate the pharmacokinetics (PK) of enteric-coated mycophenolate sodium (EC-MPS) by quantification of the active metabolite of mycophenolic acid (MPA) after multiple escalating oral doses in Han kidney transplant recipients. A total of 28 Han postoperative kidney transplant recipients were given a multiple-dose of 540, 720 or 900 mg of EC-MPS two times a day in combination with tacrolimus for 6 days. Blood specimens were collected at each time point from 0 to 12 h after EC-MPS administration. MPA plasma concentrations were measured by UPLCUV. The relationship between the EC-MPS dose and its PK parameters was assessed. In the range from 540 to 900 mg, Cmax and AUC012h did not increase with dose escalation. The AUC012h, Cmax, C0 and Tmax for the 540 720 and 900 mg doses were not significantly different, respectively (P >0.05). AUC012 h and Cmax were increased less than proportionally with increasing EC-MPS dose levels. Inter-individual variability in AUC012h, Cmax and C0 were considerable. Nonlinear PK relationships were found from the doses of 540-900 mg of EC-MPS.

Graphical abstractThis research investigated the pharmacokinetics (PK) of enteric-coated mycophenolate sodium (EC-MPS) by quantification of the active metabolite of mycophenolic acid (MPA) after multiple escalating oral doses in Han kidney transplant recipients. Nonlinear PK properties were discovered at doses ranging from 540 to 900 mg after multiple-dose administration. This may have important contributions to clinical practice. Download high-res image (121KB)Download full-size image