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 UPLC—UV. The relationship between the EC-MPS dose and its PK parameters was assessed. In the range from 540 to 900 mg, C(max) and AUC(0—12h) did not increase with dose escalation. The AUC(0—12h), C(max), C(0) and T(max) for the 540 720 and 900 mg doses were not significantly different, respectively (P >0.05). AUC(0—12 h) and C(max) were increased less than proportionally with increasing EC-MPS dose levels. Inter-individual variability in AUC(0—12h), C(max) and C(0) were considerable. Nonlinear PK relationships were found from the doses of 540–900 mg of EC-MPS.