The rationale for and limitations of therapeutic drug monitoring for mycophenolate mofetil in transplantation.

摘要

The addition of mycophenolate mofetil (MMF) to calcineurin inhibitor-based regimens reduces the incidence of acute rejection after kidney transplantation. The interpatient variability, changes over time of pharmacokinetic parameters, and the potential for drug interactions make the systemic exposure of mycophenolic acid (MPA) unpredictable at a fixed-dose regimen. An increase in plasma concentration of MPA significantly correlates with a decreased likelihood of an acute rejection after kidney or heart transplantation; therefore, a strategy of therapeutic drug monitoring for MMF therapy could improve outcome. Two large randomized, multicenter, prospective trials investigating the added value of therapeutic drug monitoring for MPA, by comparing fixed-dose treatment with concentration-controlled MMF treatment in kidney transplant recipients, are currently ongoing. More data are needed to fully establish the meaning of the reported prognostic value of preoperative inosine monophosphate dehydrogenase (IMPDH) activity, and longitudinal studies monitoring IMPDH activity after transplantation are eagerly awaited.