Evaluation of the area under the curve of enteric-coated mycophenolate sodium using a limited sampling strategy in Chinese kidney transplant recipients

Aims: To investigate the area under the curve (AUC) of mycophenolic acid (MPA) in adult Chinese renal allograft recipients receiving concomitant enteric-coated mycophenolate sodium (EC-MPS) and cyclosporine (CsA) during the early post-transplant phase and to develop optimal model equations for estimation of the MPA area under the plasma concentration-time curve from 0 to 12 hours (AUC(0-12h)) using a limited-sampling strategy (LSS). Methods: The present study enrolled 24 Chinese renal recipients treated with EC-MPS, CsA, and corticosteroid, from whom 24 serial blood samples were collected over 12 hours. MPA concentration was evaluated with enzyme multiplied immunoassay technique (EMIT). LSS was developed by multiple stepwise regression analysis using a two-group method (test group, n = 12; and validation group, n = 12). Results: The MPA predose concentration had a poor correlation with MPA AUC(0-12h), and the best equations obtained from the test group were the following: 25.73 + 0.59 x C1.5 + 0.79 x C2 + 2.03 x C4 (for three time points, r(2) = 0.761) and 22.13 + 1.7 x C0.5 + 0.61 x C1.5 + 0.78 x C2 + 1.83 x C4 (for four time points, r(2) = 0.853). When these equations were tested in the validation group, there were no significant differences in prediction errors. Conclusion: An LSS using time points at 1.5, 2, and 4 hours or 0.5, 1.5, 2, and 4 hours provides the most accurate and reliable estimation of the MPA AUC0-12h in Chinese adult renal recipients treated concomitantly with EC-MPS and CsA during the early post-transplant phase.